RU2128181C1 - 13-substituted 5-oxime derivatives of milbemycin and antihelmintic, acaricidal and insecticidal composition containing said derivatives - Google Patents

Abstract

FIELD: medicine. SUBSTANCE: present invention describes milbemycin 5-oxime derivatives of formula I:

wherein R₁ is methyl, ethyl, propyl, isopropyl or sec.butyl; X is carbonyl or methylene; Z is =C=(R²)₂ or =C=(CH₂)_n; R² is C_1-3 alkyl, and n is 0 or 1; R⁴-C(O)-N(R⁵)- (iii) is R⁶(R⁷)N-C(Y)-N(R⁵)- (iv), alkylamino, dialkylamino, alkoxyl, alkoxyalkoxyl; groups of formula III

, IV

, V R⁸SO₂-N(R⁵)- (vii), VI R⁹O-C(O)-N(R⁵)- (viii), VII R³-, VIII NO₂, NH₂; R⁴ is C_1-6 alkyl, substituted C_1-6 alkyl, substituted by alkyl C_3-6; C_2-6 alkenyl, C_2-6 alkynyl, cabocyclic C_6-1 aryl group optionally substituted by halogen, OH, CN, NO₂, C_1-4 alkyl, C_1-4 alkoxy, C_2-5 alkoxycarbonyl (other definitions are recited in claim 1) or salts thereof. Derivative have antihelmintic, acaricidal and insecticidal activity. EFFECT: improved properties of the composition. 142 ex, 1 tbl

Description

 The subject of the present invention are new 13-substituted derivatives of 5-oxime milbemycin, which have useful acaricidal, insecticidal and anthelmintic effects. This invention also provides compositions comprising these compounds and methods for their preparation.

 There are several classes of known compounds with a structure based on a 16-membered macrolide ring, which are obtained by fermentation of various microorganisms or the formation of derivatives of natural fermentation products by chemical methods. These compounds have a pronounced acaricidal, insecticidal, anthelmintic and antiparasitic effect. Examples of two classes of such compounds are milbemycins and avermectins, but there are other similar compounds that have previously been given different names or code numbers. The names of these macrolide compounds were usually derived from the names or code numbers of microorganisms of similar species found in natural conditions, after which they were extended to chemical derivatives of the same class, which caused the lack of a standardized systematic nomenclature for such compounds.

в которой R^a и R^b - атомы углерода.To avoid confusion, a standardized nomenclature system will be used in this description, created in accordance with the generally accepted rules for naming derivatives of organic compounds based on the recommendations of the International Union of Theoretical and Applied Chemistry (IUPEC), Department of Organic Chemistry, and the Commission on the Nomenclature of Organic Chemistry, which is based on a hypothetical the parent compound, defined as "milbemycin" and represented by the following formula (A):

in which R ^a and R ^b are carbon atoms.

 In order to avoid misunderstandings, the above formula (A) numbered the positions in the macrolide ring system that are most relevant to the compounds of the present invention.

Naturally formed milbemycins are macrolide compounds that are known to have anthelmintic, acaricidal and insecticidal effects. Milbemycin D is disclosed in US Pat. No. 4,346,171, where it is defined as “Compound B-41 D,” and milbemycins A ₃ and A ₄ are disclosed in US Pat. No. 3,950,360. These compounds may be expressed by the above formula (A) in which R ^a at position 13 represents a hydrogen atom, and R ^b at position 25 represents a methyl group, an ethyl group or an isopropyl group, these compounds being respectively designated milbemycin A ₃ , milbemycin A ₄ and milbemycin D. An analog of milbemycin having a carbon atom at position 13 and substituted at position 25 sec-butyl group th, is discussed in US Pat. No. 4,173,571, where it is referred to as "13-deoxy-22,23-dihydro-avermectin B _1a aglycon".

 In addition, various derivatives of the original milbemycins and avermectins were obtained, which were subjected to a comprehensive study. For example, 5-esterified milbemycins are described in US Pat. Nos. 4,201,861, N 4,206,205, N 4,173,571, N 4,171,314, N 4,203,976, N 4,289,760, N 4,459,920, N 4,579,864 and N 4,547,491, in European Patent Publications Nos. N 180539 and N 184989, as well as in patent applications of Japan, submitted to the public, N 57-120589 and 59-16894.

 Derivatives of 13-hydroxy-5-ketomylbemycin are disclosed in US Pat. No. 4,423,209. Derivatives of 5-oxime milbemycin are described in US Pat. No. 4,547,520 and European Patent Publication No. 203832.

 Milbemycins having an ester bond at position 13 are particularly interesting for the present invention. A number of compounds in which the 13-hydroxyl group in the compounds of the above formula (A) has been esterified is discussed in Japanese Patent Application No. Sho 61-180787, which describes esters of various carboxylic acids, in particular alkanoic acids. Other milbemycin derivatives having an ester bond at position 13 are described in Japanese Patent Application No. Hei 1-104078. This application contemplates compounds in which the carboxylic acid moiety has a side chain, for example, an alkyl group, at the α-position of the carboxylic acid group.

 The closest prototype of the present invention is, in our opinion, US patent N 4963582 (equivalent to European patent N 246739), which considers a number of 13-ester derivatives. However, these compounds differ from the compounds of the present invention in the nature of the group at position 13.

 The various classes of macrolide compounds discussed above that are directly related to milbemycin typically have the properties of one or more antibiotic, anthelmintic, ectoparasiticidal, acaricidal or other pesticidal agents. However, there remains a need for such products with a stronger effect against one or more types of agricultural and garden pests.

 It was found that the effect of such derivatives of milbemycin can be improved by selecting the necessary combination of substituents in the macrolide ring system, in particular, substituents at position 13. In addition, it was found that the effect of such compounds can be enhanced by the appropriate selection of certain specific ester groups at position 13, as described below. Typically, the compounds of the present invention have a stronger pesticidal effect compared to known compounds, with many compounds having a much more pronounced effect. The compounds of the present invention make flea control much more effective than the known compounds described in US Pat. No. 4,963,582.

 The aim of the present invention is to obtain macrolide compounds with a stronger effect.

 Another objective of the present invention is to provide methods for producing such compounds.

 Another objective of the present invention is to obtain pesticidal compositions and the creation of methods for their use.

 Other objectives and advantages will become apparent from the following description of the invention.

в которой R¹ - метильная группа, этильная группа, изопропильная группа или втор-бутильная группа;
X - карбонильная группа или метиленовая группа;
Z - группа формулы (i) или (ii);
=C=(R²)₂ (i)
=C=(CH₂)_m (ii)
где R² представляет алкильную группу с 1-3 атомами углерода;
m означает целое число от 2 до 5;
n означает 0 или 1;
R³ - нитрогруппа, аминогруппа, (C₁-C₄ алкил)аминогруппа, ди(C₁-C₄ алкил)аминогруппа, алкоксильная группа с 1-4 атомами углерода, (C₁-C₃ алкокси)-(C₂-C₃ алкокси)группа или группа формулы (iii), (iv), (v), (vi), (vii), (viii) или (ix):

в которых R⁴ - алкильная группа с 1-6 атомами углерода, замещенная алкильная группа с 1-6 атомами углерода, которая замещена по крайней мере одним заместителем, выбираемым из группы, включающей указанные ниже заместители α, , циклоалкильная группа с 3-6 атомами углерода, циклоалкильная группа с 3-10 атомами углерода, которая замещена по крайней мере одним заместителем, выбираемым из группы, включающей указанные ниже заместители β,/ , алкенильная группа с 2-6 атомами углерода, алкинильная группа с 2-6 атомами углерода, карбоциклическая арильная группа с 6-14 атомами углерода в кольце, которая может быть не замещена или замещена по крайней мере одним заместителем, выбираемым из группы, включающей указанные ниже заместители γ, и гетероциклическая группа с 3-6 атомами в кольце, из которых по крайней мере один является гетероатомом, выбираемым из группы, включающей гетероатомы азота, кислорода или серы, причем указанная гетероциклическая группа может быть не замещена или замещена по крайней мере одним заместителем, выбираемым из группы, включающей указанные ниже заместители γ или атомы кислорода (для образования оксогруппы);
R⁵ - атом водорода или алкильная группа с 1-4 атомами углерода;
R⁶ - атом водорода, алкильная группа с 1-6 атомами углерода или циклоалкильная группа с 3-6 атомами углерода;
R⁷ - алкильная группа с 1-6 атомами углерода, циклоалкильная группа с 3-6 атомами углерода, карбоциклическая арильная группа с 6-14 атомами углерода в кольце, которая может быть не замещена или замещена по крайней мере одним заместителем, выбираемым из группы, включающей указанные ниже заместители γ, , или аралкильная группа, в которой арильная часть является карбоциклической и имеет от 6 до 10 атомов углерода в кольце, а алкильная часть содержит от 1 до 4 атомов углерода; или
R⁶ и R⁷ вместе с атомом азота, к которому они присоединены, образуют гетероциклическое кольцо, имеющее от 3 до 6 атомов в кольце;
Y - атом кислорода или атом серы;
r означает 1, 2 или 3;
Q - метиленовая группа или карбонильная группа;
R⁸ - алкильная группа с 1-4 атомами углерода или карбоциклическая арильная группа с 6-10 атомами углерода, которая может быть не замещена или замещена по крайней мере одним заместителем, выбираемым из группы, включающей указанные ниже заместители γ;
R⁹ - алкильная группа с 1-6 атомами углерода, циклоалкильная группа с 3-6 атомами углерода, карбоциклическая арильная группа с 6-10 атомами углерода в кольце, которая может быть не замещена или замещена по крайней мере одним заместителем, выбираемым из группы, включающей указанные ниже заместители γ, или аралкильная группа, в которой арильная часть является карбоциклической и имеет от 6 до 10 атомов углерода в кольце, а алкильная часть содержит от 1 до 4 атомов углерода;
R¹⁰ - гетероциклическая группа с 3-6 атомами в кольце, из которых по крайней мере один является гетероатомом, выбираемым из группы, включающей гетероатомы азота, кислорода и серы, причем указанная гетероциклическая группа может быть не замещена или замещена по крайней мере одним заместителем, выбираемым из группы, включающей указанные ниже заместители β и атомы кислорода (для образования оксогруппы);
R¹¹ - алкильная группа с 1-3 атомами углерода;
заместители α выбирают из группы, включающей атомы галогенов, цианогруппы, алкоксильные группы с 1-4 атомами углерода, алкилтиогруппы с 1-4 атомами углерода, алкилсульфонильные группы с 1-4 атомами углерода, алканоилоксигруппы с 2-5 атомами углерода, алкоксикарбонильные группы с 2-5 атомами углерода, карбоциклические арилоксигруппы с 6-10 атомами углерода в кольце, карбоциклические арилтиогруппы с 6-10 атомами углерода в кольце, карбоциклические арилсульфонильные группы с 6-10 атомами углерода в кольце, аминогруппы, алканоиламиногруппы с 2-5 атомами углерода, N(C₂-C₅ алканоил)-N-(C₁-C₃ алкил)аминогруппы, галогеналканоиламиногруппы с 2-5 атомами углерода, алкоксикарбониламиногруппы с 2-5 атомами углерода, N(C₂-C₅ алкоксикарбонил)-N(C₁-C₃ алкил)аминогруппы), галогеналкоксикарбониламиногруппы с 2-5 атомами углерода; карбоциклические арилкарбониламиногруппы, в которых арильная часть имеет от 6 до 10 атомов углерода в кольце, аралкилкарбониламиногруппы, в которых арильная часть является карбоциклической и имеет от 6 до 10 атомов углерода в кольце, а алкильная часть содержит от 1 до 4 атомов углерода, карбоциклические арильные группы с 6-10 атомами углерода в кольце, которые могут быть не замещены или замещены по крайней мере одним заместителем, выбираемым из группы, включающей заместители γ, группы R^h, где R^h представляет гетероциклическую группу с 3-6 атомами в кольце, из которых по крайней мере один является гетероатомом, выбираемым из группы, включающей гетероатомы азота, кислорода и серы, причем указанная гетероциклическая группа может быть не замещена или замещена по крайней мере одним заместителем, выбираемым из группы, включающей указанные ниже заместители γ и атомы кислорода (для образования оксогруппы), группы формулы R^h-S-, где R^h имеет указанные выше значения; алканоильные группы с 2-5 атомами углерода и аралкилоксикарбониламиногруппы, в которых арильная часть является карбоциклической и имеет от 6 до 10 атомов углерода, а алкильная часть содержит от 1 до 4 атомов углерода;
заместители β выбирают из группы, включающей атомы галогенов, алкоксильные группы с 1-4 атомами углерода и алканоилоксигруппы с 2-5 атомами углерода;
заместители γ выбирают из группы, включающей атомы галогенов, гидроксильные группы, цианогруппы, нитрогруппы, алкильные группы с 1-4 атомами углерода, алкоксильные группы с 1-4 атомами углерода и алкоксикарбонильные группы с 2-5 атомами углерода;
заместители δ выбирают из группы, включающей аминогруппы, алканоиламиногруппы с 2-5 атомами углерода, галогеналканоиламиногруппы с 2-5 атомами углерода и алкоксикарбониламиногруппы с 2-6 атомами углерода;
и их соли.The present invention provides compounds of formula (I):

in which R ¹ is a methyl group, an ethyl group, an isopropyl group or a sec-butyl group;
X is a carbonyl group or a methylene group;
Z is a group of formula (i) or (ii);
= C = (R ² ) ₂ (i)
= C = (CH ₂ ) _m (ii)
where R ² represents an alkyl group with 1-3 carbon atoms;
m is an integer from 2 to 5;
n is 0 or 1;
R ³ - nitro group, amino group, (C ₁ -C ₄ alkyl) amino group, di (C ₁ -C ₄ alkyl) amino group, alkoxy group with 1-4 carbon atoms, (C ₁ -C ₃ alkoxy) - (C ₂ - C ₃ alkoxy) group or group of the formula (iii), (iv), (v), (vi), (vii), (viii) or (ix):

in which R ⁴ is an alkyl group with 1-6 carbon atoms, a substituted alkyl group with 1-6 carbon atoms, which is substituted by at least one substituent selected from the group consisting of the following substituents α, and a cycloalkyl group with 3-6 atoms carbon, cycloalkyl group with 3-10 carbon atoms, which is substituted by at least one substituent selected from the group consisting of the following substituents β, /, alkenyl group with 2-6 carbon atoms, alkynyl group with 2-6 carbon atoms, carbocyclic aryl groups with 6-14 carbon atoms in the ring, which may be unsubstituted or substituted by at least one substituent selected from the group consisting of the following substituents γ, and a heterocyclic group with 3-6 atoms in the ring, of which at least one is a heteroatom selected from the group consisting of nitrogen, oxygen or sulfur heteroatoms, wherein said heterocyclic group may be unsubstituted or substituted by at least one substituent selected from the group consisting of the following substituents γ or acid atoms genus (for the formation of an oxo group);
R ⁵ is a hydrogen atom or an alkyl group with 1-4 carbon atoms;
R ⁶ is a hydrogen atom, an alkyl group with 1-6 carbon atoms or a cycloalkyl group with 3-6 carbon atoms;
R ⁷ is an alkyl group with 1-6 carbon atoms, a cycloalkyl group with 3-6 carbon atoms, a carbocyclic aryl group with 6-14 carbon atoms in the ring, which may be unsubstituted or substituted by at least one substituent selected from the group, including the following substituents γ,, or an aralkyl group in which the aryl part is carbocyclic and has from 6 to 10 carbon atoms in the ring and the alkyl part contains from 1 to 4 carbon atoms; or
R ⁶ and R ⁷ together with the nitrogen atom to which they are attached form a heterocyclic ring having from 3 to 6 atoms in the ring;
Y is an oxygen atom or a sulfur atom;
r is 1, 2 or 3;
Q is a methylene group or a carbonyl group;
R ⁸ is an alkyl group with 1-4 carbon atoms or a carbocyclic aryl group with 6-10 carbon atoms, which may be unsubstituted or substituted by at least one substituent selected from the group consisting of the following substituents γ;
R ⁹ is an alkyl group with 1-6 carbon atoms, a cycloalkyl group with 3-6 carbon atoms, a carbocyclic aryl group with 6-10 carbon atoms in the ring, which may be unsubstituted or substituted by at least one substituent selected from the group, including the following substituents γ, or an aralkyl group in which the aryl part is carbocyclic and has from 6 to 10 carbon atoms in the ring, and the alkyl part contains from 1 to 4 carbon atoms;
R ¹⁰ is a heterocyclic group with 3-6 atoms in the ring, of which at least one is a heteroatom selected from the group consisting of nitrogen, oxygen and sulfur heteroatoms, said heterocyclic group being optionally substituted or substituted by at least one substituent, selected from the group consisting of the following substituents β and oxygen atoms (to form an oxo group);
R ¹¹ is an alkyl group with 1-3 carbon atoms;
substituents α are selected from the group consisting of halogen atoms, cyano groups, alkoxy groups with 1-4 carbon atoms, alkylthio groups with 1-4 carbon atoms, alkylsulfonyl groups with 1-4 carbon atoms, alkanoyloxy groups with 2-5 carbon atoms, alkoxycarbonyl groups with 2 -5 carbon atoms, carbocyclic aryloxy groups with 6-10 carbon atoms in the ring, carbocyclic arylthio groups with 6-10 carbon atoms in the ring, carbocyclic arylsulfonyl groups with 6-10 carbon atoms in the ring, amino groups, alkanoylamino groups with 2-5 atoms and carbon, N (C ₂ -C ₅ alkanoyl) -N- (C ₁ -C ₃ alkyl) amino groups, haloalkanoylamino groups with 2-5 carbon atoms, alkoxycarbonylamino groups with 2-5 carbon atoms, N (C ₂ -C ₅ alkoxycarbonyl) -N (C ₁ -C ₃ alkyl) amino groups), haloalkoxycarbonylamino groups with 2-5 carbon atoms; carbocyclic arylcarbonylamino groups in which the aryl part has 6 to 10 carbon atoms in the ring, aralkylcarbonylamino groups in which the aryl part is carbocyclic and has 6 to 10 carbon atoms in the ring, and the alkyl part contains from 1 to 4 carbon atoms, carbocyclic aryl groups with 6-10 carbon atoms in the ring, which may be unsubstituted or substituted by at least one substituent selected from the group consisting of γ substituents, of the group R ^h , where R ^h represents a heterocyclic group with 3-6 atoms in a ring of which at least one is a heteroatom selected from the group consisting of nitrogen, oxygen and sulfur heteroatoms, said heterocyclic group being optionally substituted or substituted by at least one substituent selected from the group consisting of the following substituents γ and oxygen atoms (to form an oxo group), groups of the formula R ^h —S—, where R ^h is as defined above; alkanoyl groups with 2-5 carbon atoms and aralkyloxycarbonylamino groups in which the aryl part is carbocyclic and has from 6 to 10 carbon atoms, and the alkyl part contains from 1 to 4 carbon atoms;
substituents β are selected from the group consisting of halogen atoms, alkoxy groups with 1-4 carbon atoms and alkanoyloxy groups with 2-5 carbon atoms;
substituents γ are selected from the group consisting of halogen atoms, hydroxyl groups, cyano groups, nitro groups, alkyl groups with 1-4 carbon atoms, alkoxy groups with 1-4 carbon atoms and alkoxycarbonyl groups with 2-5 carbon atoms;
substituents δ are selected from the group consisting of amino groups, an alkanoylamino group with 2-5 carbon atoms, a haloalkanoylamino group with 2-5 carbon atoms and an alkoxycarbonylamino group with 2-6 carbon atoms;
and their salts.

 The present invention further provides an anthelmintic, acaricidal and insecticidal composition containing an anthelmintic, acaricidal or insecticidal compound in a mixture with a filler or diluent suitable for use in agriculture or horticulture, characterized in that said compound is selected from the group consisting of compounds of formula (I) and their salts.

 The present invention also includes a method of protecting plants and animals, including humans, from damage by parasites such as ticks, helminths and insects, in accordance with which the active compound treats plants or animals, individual parts or reproductive material (e.g. seeds) of said plants, the lesion of plants or animals, individual parts or seeds of such plants, while the active compound is selected from the group comprising compounds of formula (I) or their salts.

In the compounds of the present invention, R ¹ may represent a methyl, ethyl, isopropyl or sec-butyl group. Of these, methyl and ethyl groups are preferred, with the ethyl group being most preferred.

 X represents a methylene or carbonyl group, of which carbonyl group is preferred.

If Z represents a group of the formula> C = (R ² ) ₂ , and R ^{2 is} an alkyl group with 1-3 carbon atoms, such a group may have a straight or branched chain with 1-3 carbon atoms, that is, it can be methyl, ethyl, propyl and isopropyl groups, of which methyl group is preferred.

If Z is a group of the formula = C = (CH ₂ ) _m , m may mean an integer from 2 to 5, that is, 2, 3, 4 or 5, in which case Z represents a spirocycloalkyl group, in particular cyclopropyl, cyclobutyl, cyclopentyl or a cyclohexyl group. Of these, cyclopropyl and cyclobutyl groups are preferred.

If R ³ is a (C ₁ -C ₄ alkyl) amino group, the alkyl part of this group may have a straight or branched chain; examples of such groups include methylamino, ethylamino, propylamino, isopropylamino, butylamino, isobutylamino, sec-butylamino and tert-butylamino groups, of which methylamino, ethylamino, propylamino and butylamino groups are preferred, with methylamino being the most preferred.

If R ³ is a di (C ₁ -C ₄ alkyl) amino group, then the two alkyl groups may be the same or different and may represent straight or branched chain groups having from 1 to 4 carbon atoms. Examples of such groups include dimethylamino, diethylamino, dipropylamino, diisopropylamino, dibutylamino, diisobutylamino, di-sec-butylamino, di-tert-butylamino, N-methyl-N-ethylamino, N-methyl-N-propylamino, N-methyl-N- isopropylamino, N-methyl-N-butylamino, N-methyl-N-isobutylamino, N-methyl-N-sec-butylamino, N-methyl-N-tert-butylamino, N-ethyl-N-propylamino, N-ethyl- N-isopropylamino, N-ethyl-N-butylamino, N-ethyl-N-isobutylamino, N-ethyl-N-sec-butylamino, Ethyl-N-tert-butylamino, N-propyl-N-isopropylamino, N- propyl-N-butylamino, N-propyl-N-isobutylamino, N-propyl-N-sec-butyl mino, N-propyl-N-tert-butylamino, N-isopropyl-N-isobutylamino, N-isopropyl-N-sec-butylamino, N-isopropyl-N-tert-butylamino, N-butyl-N-isobutylamino, N-butyl-N-sec-butylamino, N-butyl-N-tert-butylamino, N-isobutyl-N-sec-butylamino, N-isobutyl-N-tert-butylamino and N-sec-butyl-N-tert-butyl butylamino groups, of which preference is given to those groups in which the two alkyl groups are the same, in particular dimethylamino, diethylamino, dipropylamino and dibutylamino groups, of which dimethylamino and diethylamino groups are most preferred.

If R ³ is an alkoxy group with 1-4 carbon atoms, it may have a straight or branched chain with 1-4 carbon atoms and represent methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy and tert-butoxy, from of which methoxy, ethoxy, propoxy and butoxy are preferred, with methoxy and ethoxy being more preferred, and methoxy is most preferred.

If R ³ is a (C ₁ -C ₃ alkoxy) - (C ₂ -C ₃ alkoxy) group, then each alkoxy group may have a straight or branched chain with 1-3 or 2 or 3 carbon atoms and may be selected from the above alkoxyl groups. Examples of such alkoxy-alkoxy groups include 1-methoxyethoxy, 1-ethoxyethoxy, 1-propoxyethoxy, 1-isopropoxyethoxy, 1-butoxyethoxy, 1-isobutoxyethoxy, 1-sec-butoxyethoxy, 1-tert-butoxyethoxy, 2-methoxyethoxy, 2-ethoxyethoxy , 2-propoxyethoxy, 2-isopropoxyethoxy, 2-butoxyethoxy, 2-isobutoxyethoxy, 2-sec-butoxyethoxy, 2-tert-butoxyethoxy, 1-methoxypropoxy, 1-ethoxypropoxy, 1-propoxypropoxy, 1-isopropoxypropoxy, 1-butoxypropoxy, 1 -isobutoxypropoxy, 1-sec-butoxypropoxy, 1-tert-butoxypropoxy, 2-methoxypropoxy, 2-ethoxyprop xi, 2-propoxypropoxy, 2-isopropoxypropoxy, 2-butoxypropoxy, 2-isobutoxypropoxy, 2-sec-butoxypropoxy, 2-tert-butoxypropoxy, 3-methoxypropoxy, 3-ethoxypropoxy, 3-propoxypropoxy, 3-isopropoxypropoxy, 3-but 3-isobutoxypropoxy, 3-sec-butoxypropoxy and 3-tert-butoxypropoxy groups, of which 2-methoxyethoxy, 2-ethoxyethoxy, 2-propoxyethoxy, 2-isopropoxyethoxy, 2-butoxyethoxy, 2-isobutoxyethoxy, 2-sec-butoxyethoxy and 2-tert-butoxyethoxy groups, with 2- methoxyethoxy group.

и R⁴ представляет алкильную группу с 1-6 атомами углерода, она может иметь прямую или разветвленную цепь с 1-6 атомами углерода; примеры такой группы включают метил, этил, пропил, изопропил, бутил, изобутил, втор-бутил, трет-бутил, пентил, изопентил, неопентил, 2-метилбутил, 2-этил- пропил, 4-метилпентил, 3-метилпентил, 2-метилпентил, 1-метилпентил, 3,3-диметилбутил, 2,2-диметилбутил, 1,1-диметилбутил, 1,2-диметилбутил, 1,3-диметилбутил, 2,3-диметилбутил, 2-этилбутил, гексил и изогексил. Из них предпочтение отдается алкильным группам с 1-4 атомами углерода, в частности метильной, этильной, пропильной, изопропильной, бутильной и изобутильной группам, более предпочтительными являются метильная и этильная группы и самой предпочтительной считается метильная группа. Группами формулы (iii) являются алканоиламиногруппы с 2-7, предпочтительно 2 или 3 атомами углерода, поэтому группами формулы (iii), в которых, R⁴ представляет метильную или этильную группу, являются соответственно ацетиламино и пропиониламиногруппы.If R ³ is a group of formula (iii):

and R ⁴ represents an alkyl group with 1-6 carbon atoms, it may have a straight or branched chain with 1-6 carbon atoms; examples of such a group include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 2-methylbutyl, 2-ethylpropyl, 4-methylpentyl, 3-methylpentyl, 2- methylpentyl, 1-methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 2-ethylbutyl, hexyl and isohexyl. Of these, alkyl groups with 1-4 carbon atoms are preferred, in particular methyl, ethyl, propyl, isopropyl, butyl and isobutyl groups, methyl and ethyl groups are more preferred and a methyl group is most preferred. The groups of formula (iii) are alkanoylamino groups with 2-7, preferably 2 or 3 carbon atoms, therefore the groups of formula (iii), in which R ⁴ represents a methyl or ethyl group, are respectively acetylamino and propionylamino groups.

If R ³ is a group of formula (iii), and R ⁴ represents a substituted alkyl group with 2-6 carbon atoms, which is substituted by at least one substituent selected from the group consisting of the above substituents α, the alkyl group may have a straight or branched chain with 1-6 carbon atoms; examples include the above unsubstituted alkyl groups. Below are examples of groups and atoms included in the number of substituents α. As mentioned above, the group of formula (iii) is an alkanoylamino group with 2-7 carbon atoms, which in this case is substituted by at least one substituent selected from the group consisting of substituents α. Typical examples of such alkanoylamino groups represented by R ³ include:
halogenated alkanoylamino of 2-7 carbon atoms, especially halogenated acetylamino groups (such as the chloroacetyl amino, dihloratsetilamino, trihloratsetilamino, bromatsetilamino, ftoratsetilamino, and diftoratsetilamino triftoratsetilaminogruppy), halogenated propionylamino group (such as 3-hlorpropionilamino, dihlorpropionilamino 3, 3 and 3 trihlorpropionilamino trifluoropropionylamino groups), halogenated butyrylamino groups (such as 4-chlorobutyrylamino, 4-dichlorobutyrylamino, 4-trichlorobutyrylamino and 4-trifluorobutyl amylamino groups), halogenated pentanoylamino groups (such as 5-chloropentanoylamino, 5-dichloropentanoylamino, 5-trichloropentanoylamino and 5-triforopentanoylamino groups), halogenated hexanoylamino groups (such as 6-chlorohexanoylamino, 6-hexano-hetero-organo-6-hetero-organo-6-hetero-organo-6-hetero-organo-6-hetero-oxo-6-hetero-organo-6-hetero-organo-6-hetero-organo-6-hetero-organo-6-hetero-organo-6-hetero-organo-amino such as 7-chlorheptanoylamino, 7-dichloroheptanoylamino, 7 trichloroheptanoylamino and 7-trifluoroheptanoylamino groups), of which halogenated acetylamino is preferred ruppam, in particular chloroacetylamino, bromoacetylamino, difluoroacetylamino and trifluoroacetylamino groups);
cyano-substituted alkanoylamino groups with 2 to 7 carbon atoms, in particular cyano-substituted acetylamino groups, such as a cyanoacetylamino group, cyano-substituted propionylamino groups, 3-cyanopropionylamino groups, cyano-substituted butyrylamino-cyanoamino-cyanoamino-cyanoamino A 6-cyanhexanoylamino group and cyano-substituted heptanoylamino groups such as a 7-cyanheptanoylamino group; of these, preference is given to cyano-substituted acetylamino groups, in particular to a cyanoacetylamino group;
alkylthio-substituted alkanoylamino groups with 2-7 carbon atoms, in particular alkylthio-substituted acetylamino groups [such as methyl thioacetylamino, di (methylthio) acetylamino, tri (methylthio) acetylamino, propylthioacetylamino, ethylthioamino-thioamino (thioamino-thioamino) [such as 3-methylthiopropionylamino and 3-di (methylthio) propionylamino groups], alkylthio substituted butyrylamino groups [such as 4-methylthiobutyrylamino and 4-di (methylthio) butyrylamino groups], alkylthio substituted s pentanoilaminogruppy [such as 5-metiltiopentanoilamino and 5-di (methylthio) pentanoilaminogruppy] alkylthio substituted hexanoylamino groups [such as the 6-metiltiogeksanoilamino and 6-di (methylthio) hexanoylamino groups], and alkylthio geptanoilaminogruppy [such as the 7-metiltiogeptanoilamino and 7-di (methylthio ) heptanoylamino groups], of which alkylthio substituted acetylamino groups are preferred, in particular methylthioacetylamino, propylthioacetylamino and di (ethylthio) acetylamino groups;
alkilsulfonilzameschennye alkanoylamino of 2-7 carbon atoms, in particular alkilsulfonilzameschennye acetylamino groups [such as metilsulfonilatsetilamino, di (methylsulphonyl) acetylamino, tri (methylsulphonyl) acetylamino, propilsulfonilatsetilamino, etilsulfonilatsetilamino, di (ethylsulphonyl) acetylamino and tri (ethylsulphonyl) acetylamino groups], alkilsulfonilzameschennye propionylamino [ such as 3-methylsulfonylpropionylamino and 3-di (methylsulfonyl) propionylamino groups], alkylsulfonyl substituted butyrylamino groups [ta such as 4-methylsulfonylbutyrylamino and 4-di (methylsulfonyl) butyrylamino groups], alkylsulfonyl-substituted pentanoylamino groups [such as 5-methylsulfonylpentanoylamino and 5-di (methylsulfonyl) pentanoyl-amino-6-substituted-methyl-6-substituted-methyl-6-substituted-methyl-6-substituted-methyl-substituted-methyl-6-methyl-substituted-methyl-substituted-methyl-substituted-methyl-substituted-methyl-substituted-methyl-substituted-methyl-substituted-methyl) and alkylsulfonyl substituted heptanoylamino groups [such as 7-methylsulfonylheptanoylamino and 7-di (methylsulfonyl) heptanoylamino groups], of which alkylsulfonyls are preferred further acetylamino groups, in particular methylsulfonylacetylamino, propylsulfonylacetylamino and di (ethylsulfonyl) acetylamino groups;
alkanoiloksizameschennye alkanoylamino of 2-7 carbon atoms, in particular alkanoiloksizameschennye acetylamino groups (such as the acetoxyacetylamino, and propioniloksiatsetilamino butiriloksiatsetilaminogruppy) alkanoiloksizameschennye propionylamino group (such as 3-atsetoksipropionilaminogruppa) alkanoiloksizameschennye groups (such as the 4-atsetoksibutirilaminogruppa) alkanoiloksizameschennye pentanoilaminogruppy (such as 5- acetoxypentanoylamino group), alkanoyloxy substituted hexanoylamino groups (such as 6-acetoxyhexano laminogruppa) and alkanoiloksizameschennye geptanoilaminogruppy (such as 7- atsetoksigeptanoilaminogruppa), of which preference is given alkanoiloksizameschennym acetylamino group, in particular acetoxyacetylamino, propioniloksiatsetilamino atsetoksipropionilaminogruppam or 3;
alkoxycarbonyl substituted alkanoylamino groups with 2-7 carbon atoms, in particular alkoxycarbonyl substituted acetylamino groups
[Metoksikarbonilatsetilamino like, and propoksikarbonilatsetilamino etoksikarbonilatsetilaminogruppy], alkoxycarbonyl-substituted propionylamino [such as 3-metoksikarbonilpropionilamino group], alkoxycarbonyl-substituted butyrylamino [such as the 4-metoksikarbonilbutirilaminogruppa], alkoxycarbonyl-substituted pentanoilaminogruppy [such as 5-metoksikarbonilpentanoilamino group], alkoxycarbonyl-substituted hexanoylamino groups [such as the 6- metoksikarbonilgeksanoilaminogruppa ] and alkoxycarbonyl substituted hepta oilaminogruppy [such as the 7-amino group metoksikarbonilgeptanoil], of which preferred alkoxycarbonyl-substituted propionylamino, in particular metoksikarbonilpropionilaminogruppe;
aryloxy-substituted alkanoylamino of 2-7 carbon atoms, especially aryloxy-substituted acetylamino groups, such as fenoksiatsetilaminogruppa, aryloxy-substituted propionylamino group, such as 3-fenoksipropionilaminogruppa, aryloxy-substituted butyrylamino groups such as 4-fenoksibutirilaminogruppa, aryloxy pentanoilaminogruppy such as 5-fenoksipentanoilaminogruppa, aryloxy-substituted hexanoylamino groups, such as 6 phenoxyhexanoylamino group, and aryloxy substituted heptanoylamino groups such as 7-phen oxyheptanoylamino groups, of which preference is given to aryloxy substituted acetylamino groups, in particular a phenoxyacetylamino group;
ariltiozameschennye alkanoylamino of 2-7 carbon atoms, in particular acetylamino ariltiozameschennye such as feniltioatsetilaminogruppa, ariltiozameschennye propionylamino group, such as 3-feniltiopropionilaminogruppa, ariltiozameschennye butyrylamino, such as 4- feniltiobutirilaminogruppa, ariltiozameschennye pentanoilaminogruppy such as 5-feniltiopentanoilaminogruppa, ariltiozameschennye hexanoylamino groups, such as 6-phenylthiohexanoylamino group, and arylthio substituted heptanoylamino groups such as 7-phenyl thioheptanoylamino groups, of which preference is given to arylthio substituted acetylamino groups, in particular a phenylthioacetylamino group;
arilsulfonilzameschennye alkanoylamino of 2-7 carbon atoms, in particular acetylamino arilsulfonilzameschennye such as fenilsulfonilatsetilaminogruppa, arilsulfonilzameschennye propionylamino group, such as 3-fenilsulfonilpropionilaminogruppa, arilsulfonilzameschennye butyrylamino, such as 4- fenilsulfonilbutirilaminogruppa, arilsulfonilzameschennye pentanoilaminogruppy such as 5-fenilsulfonilpentanoilaminogruppa, arilsulfonilzameschennye hexanoylamino groups, such as 6-phenylsulfonylhexanoyl a mino group and arylsulfonyl substituted heptanoylamino groups such as 7-phenylsulfonylheptanoylamino groups, of which arylsulfonyl substituted acetylamino groups are preferred, in particular phenylsulfonylacetylamino group;
amino substituted alkanoylamino groups with 2-7 carbon atoms, in particular amino substituted acetylamino groups, such as aminoacetylamino group, amino substituted propionylamino groups, such as 2-aminopropionylamino and 3-aminopropionylamino groups; amino substituted butyrylamino groups such as 2-aminobutyrylamino, 3-aminobutyrylamino and 4-aminobutyrylamino; amino substituted methylpropionylamino groups such as 3-amino-3-methylpropionylamino and 2-amino-2-methylpropionylamino groups; amino substituted pentanoylamino groups such as 2-aminopentanoylamino, 3-aminopentanoylamino, 4-aminopentanoylamino and 5-aminopentanoylamino; amino substituted methylbutyrylamino groups such as 2-amino-3-methylbutyrylamino and 2-amino-2-methylbutyrylamino groups; amino substituted hexanoylamino groups such as 2-aminohexanoylamino, 3-aminohexanoylamino, 4-aminohexanoylamino, 5-aminohexanoylamino and 6-aminohexanoylamino; amino substituted methylpentanoylamino groups such as 2-amino-3-methylpentanoylamino and 2-amino-4-methylpentanoylamino; amino substituted dimethyl butyrylamino groups such as 2-amino-3,3-dimethyl butyrylamino; and amino-substituted heptanoylamino groups such as 2-aminoheptanoylamino and 7-aminoheptanoylamino groups, of which amino-substituted acetylamino groups are preferred, in particular aminoacetylamino, 2-aminopropionylamino, 3-aminopropionylamino, 2-amino-2-methyl-2-methyl-2-methylpropionylamino amino-3,3 dimethylbutyrylamino and 2-amino-4-methylpentanoylamino groups; more preferred are aminoacetylamino, 2-aminopropionylamino, 3-aminopropionylamino, 2-amino-2-methylpropionylamino and 2-amino-3-methylbutyrylamino groups and the most preferred are aminoacetylamino, 2-aminopropionylamino and 3-aminopropionylamino;
(C ₂ -C ₅ alkanoyl) amino substituted C ₂ -C ₇ alkanoylamino groups, in particular substituted acetylamino groups such as (N-acetylamino) acetylamino, (N-butyrylamino) acetylamino and (N-valerylamino) acetylamino; substituted propionylamino groups such as 3- (N-acetylamino) propionylamino, 3- (N-butyrylamino) propionylamino and 3- (N-valerylamino) propionylamino; substituted butyrylamino groups such as 4- (N-acetylamino) butyrylamino, 4- (N-butyrylamino) butyrylamino and 4- (N-valerylamino) butyrylamino; substituted valerylamino groups such as 5- (N-acetylamino) valerylamino, 5- (N-butyrylamino) valerylamino and 5- (N-valerylamino) valerylamino group, of which a (N-acetylamino) acetylamino group is preferred;
N- (C ₂ -C ₅ alkanoyl) -N- (C ₁ -C ₃ alkyl) amino substituted alkanoyl amino groups in which the alkanoylamino moiety has from 2 to 7 carbon atoms, in particular substituted acetylamino groups such as (N-methyl-N-acetylamino) acetylamino, (N-ethyl-N acetylamino) acetylamino, (N-propyl-N-acetylamino) acetylamino, (N-methyl-N-butyrylamino) acetylamino, (N-ethyl-N-butyrylamino) acetyl amino, (N-propyl-N-butyrylamino) acetylamino, (N-methyl- N-valerylamino) -acetylamino, (N-ethyl-N-valerylamino) acetylamino, and (N-propyl N-valerylamino) acetylamino group; substituted propionylamino groups such as 3- (N-methyl-N-acetylamino) propionylamino, 3- (N-ethyl-N-acetylamino) propionylamino, 3- (N-propyl-N-acetylamino) propionylamino, 3- (N-methyl -N-butyrylamino) propionylamino, 3- (N-ethyl-N-butyrylamino) propionylamino, 3- (N-propyl-N-butyrylamino) propionylamino, 3- (N-methyl-N-valerylamino) propionylamino, 3- (N ethyl N-valerylamino) propionylamino and 3- (N-propyl-N-valerylamino) propionylamino groups; substituted butyrylamino groups such as 4 (N-methyl-N-acetylamino) butyrylamino, 4- (N-ethyl-N-acetylamino) butyrylamino, 4- (N-propyl-N-acetylamino) butyrylamino, 4- (N-methyl -N butyrylamino) butyrylamino, 4- (N-ethyl-N-butyrylamino) butyrylamino, 4- (N-propyl-N-butyrylamino) butyrylamino, 4- (N-methyl-N-valerylamino) butyrylamino, 4- (N ethyl N-valerylamino) butyrylamino and 4- (N propyl-N-valerylamino) butyrylamino; and substituted valeryl amino groups such as 5- (N-methyl-N-acetylamino) valelamino, 5- (N-ethyl-N-acetylamino) valerylamino, 5- (N-propyl-N-acetylamino) valerylamino, 5- (N -methyl-N-butyrylamino) valerylamino, 5- (N-ethyl-N-butyrylamino) valerylamino, 5- (N-propyl-N-butyrylamino) valerylamino, 5- (N-methyl-N-valerylamino) valerylamino, 5- (N-propyl-N-butyrylamino) valerylamino, 5- (N-methyl-N-valerylamino) valerylamino, 5- (N-ethyl-N-valerylamino) valerylamino and 5- (N-propyl-N-valerylamino) valerylamino group, of which preference is given to the (N-methyl-N-acetylamino) acetylamino group;
(C ₂ -C ₅ haloalkanoyl) amino substituted C ₂ -C ₇ alkanoylamino groups in which the alkanoyl groups may have the above meanings and the halogen atoms may be chlorine, bromine, fluorine or iodine, in particular haloalkanoylamino-substituted acetylamino groups, such as (N-chloroacetylamino) acetylamino, (N-dichloroacetylamino) acetylamino-amino-tri-amino acetylamino, (N-fluoroacetylamino) acetylamino, (N-difluoroacetylamino) acetylamino, (N-trifluoroacetylamino) acetylamino, (N-bromoacetylamino) acetylamino, (N-iodoacetylamino) acetylamino, (N-4-chlorobutyrylamino (4-acetylamino) -fluorobutyrylamino) acetyl amino and (N-5-fluoro-valerylamino) acetylamino groups; galogenalkanoilaminozameschennye propionylamino group, such as (N-hloratsetilamino) propionylamino, (N-dichloroacetyl amino) propionylamino, (N-trihloratsetilamino) propionylamino, (N- ftoratsetilamino) propionylamino, (N-diftoratsetilamino) propionylamino, (N-trifluoroacetylamino) propionylamino, (N -bromoacetylamino) propionylamino, (N-iodoacetylamino) propionylamino, (N-4-chlorobutyrylamino) propionylamino, (N-4-fluorobutyrylamino) propionylamino and (N-5-fluorovalerylamino) propionylamino group; haloalkanoylamino-substituted butyrylamino groups, such as (N-chloroacetylamino) butyrylamino, (N-dichloroacetylamino) butyrylamino, (N-trichloroacetylamino) butyrylamino, (N-fluoroacetylamino) butyrylamino, (N-difluoro-amino-trinorino-amino) bromoacetylamino) butyrylamino, (N-iodoacetylamino) butyrylamino, (N-4-chlorobutyrylamino) butyrylamino, (N-4-fluorobutyrylamino) butyrylamino and (N-5-fluorovalerylamino) butyrylamino group; and haloalkanoylamino substituted valerylamino groups such as (N-chloroacetylamino) valerylamino, (N-dichloroacetylamino) valerylamino, (N-trichloroacetylamino) valerylamino, (N-fluoroacetylamino) valerylamino, (N-difluoroacetylamino-amino (vino -bromoacetylamino) valerylamino, (N-iodoacetylamino) valerylamino, (N-4-chlorobutyrylamino) valerylamino, (N-4-fluorobutyrylamino) valerylamino and (N-5-fluorovalerylamino) valerylamino groups, of which (N-chloroacetylaminoamino) is preferred;
alkoksikarbonilaminozameschennye alkanoylamino groups in which the alkoxycarbonyl part has from 2 to 5 carbon atoms, and a part, which is alkanoylamino having 2 to 7 carbon atoms, in particular alkoksikarbonilaminozameschennye acetylamino groups [such as metoksikarbonilaminoatsetilamino, etoksikarbonilaminoatsetilamino, propoksikarbonilaminoatsetilamino, isopropoxy karbonilaminoatsetilamino, butoksikarbonilaminoatsetilamino and tert butoksikarbonilaminoatsetilaminogruppy ], alkoxycarbonylamino substituted propion laminogruppy [such as the 2-methoxycarbonylamino propionylamino, 3-metoksikarbonilaminopropionilamino, karbonilaminopropionilamino 2-ethoxy, 3-etoksikarbonilaminopropionilamino, propoksikarbonilaminopropionilamino 2-, 3- propoksikarbonilaminopropionilamino, 2-izopropoksikarbonilaminopropionilamino, 3- izopropoksikarbonilaminopropionilamino, 2-butoxycarbonyl aminopropionilamino, 3-butoksikarbonilaminopropionilamino, 2-t - butoxycarbonylaminopropionylamino and 3-tert-butoxycarbonyl aminopropionylamino], alkoxycarbonyl foreign substituted butyrylamino groups [such as 2-methoxycarbonylaminobutyrylamino, 2-ethoxycarbonylaminobutyrylamino and 4-ethoxycarbonylaminobutyrylamino groups], alkoxycarbonylamino-methyloxymethyroxymethyl-methoxy-methoxy-methoxy-2-methyloxy-methoxy-methoxy-2-methoxy-2-methoxy-2-methyl-2-methoxy-2-methyl-2-methyl-2-methoxy-2-methyl-2-methoxy-2-methyl-2-methyl-2-methoxy-2-methyl-2-methyl-2-methoxy-2-methyl-2-methoxy-methyl-2-methoxy; methylpropionylamino, 2-isopropoxycarbonylamino-2-methylpropionylamino, 2 butoxycarbonylamino-2-methylpropionylamino and 2-tert-butoxycarbonylamino-2-methylpr pionilaminogruppy] alkoksikarbonilaminozameschennye pentanoilaminogruppy [such as 5-and 5-metoksikarbonilaminopentanoilamino etoksikarbonilaminopentanoilaminogruppy] alkoksikarbonilaminozameschennye 4-metilpentanoilaminogruppy [such as the 2-methoxycarbonylamino-4-methyl-pentanoylamino and 2-ethoxycarbonylamino-4 metilpentanoilaminogruppy] alkoksikarbonilaminozameschennye izovalerilaminogruppy [such as 2- methoxycarbonylamino-3-methylbutyrylamino and 2-ethoxycarbonylamino-3-methylbutyrylamino groups], alkoxycarbonylamino substituted g eksanoilaminogruppy from [such as the 6- metoksikarbonilaminogeksanoilaminogruppa] alkoksikarbonilaminozameschennye 3,3-dimetilbutirilaminogruppy [such as the 2-methoxycarbonylamino-3,3-dimetilbutirilamino and 2- ethoxycarbonylamino-3,3-dimetilbutirilaminogruppy] and alkoksikarbonilaminozameschennye geptanoilaminogruppy [such as the 7- metoksikarbonilaminogeptanoilaminogruppa] which are preferred alkoxycarbonylamino substituted acetylamino, propionylamino, butyrylamino, isobutyrylamino, isovalerylamino, 4-methylpentanoylamino and 3,3-dime tilbutirilaminogruppam particularly metoksikarbonilaminoatsetilamino, etoksikarbonilaminoatsetilamino, tert-butoksikarbonilaminoatsetilamino, metoksikarbonilaminopropionilamino-2, 3-metoksikarbonilaminopropionilamino, metoksikarbonilaminobutirilamino-2, 2-methoxycarbonylamino-2-metilpropionilamino, 2-methoxycarbonylamino-3-methylbutyrylamino, 2-methoxycarbonylamino-4-methyl-pentanoylamino and 2- methoxycarbonylamino-3,3 dimethylbutyrylamino groups;
N- (C ₂ -C ₅ alkoxycarbonyl) -N- (C ₁ -C ₃ alkyl) amino substituted alkanoylamino groups, in particular N-alkoxycarbonyl-N-alkylamino substituted acetylamino groups [such as (N-methoxycarbonyl-N-methylamino) acetylamino, (N-ethoxycarbonyl-N-methylamino) acetylamino, (N-propoxycarbonyl-N- , (N-isopropoxycarbonyl-N-methylamino) acetylamino, (N-butoxycarbonyl-Nmethylamino) acetylamino and (N-tert-butoxycarbonyl-N-methylamino) acetylamino], N-alkoxycarbonyl-N-alkylamino substituted propionylamino groups [such as 2- ( -methoxycarbonyl-N-methylamino) propionylamino, 3- (N- methoxy arbonyl-N-methylamino) propionylamino, 2- (N-ethoxycarbonyl-N-methylamino) propionylamino, 3- (N-ethoxycarbonyl-N-methylamino) propionylamino, 2- (N-propoxycarbonyl-N-methylamino) propionylamino, 3- ( N-propoxycarbonyl-N-methylamino) propionylamino, 2- (N-isopropoxycarbonyl-N-methylamino) propionylamino, 3- (N-isopropoxycarbonyl-N-methylamino) propionylamino, 2- (N-butoxycarbonyl-N-methylamino) propionylamino, - (N-butoxycarbonyl-N-methylamino) propionylamino, 2- (N-tert-butoxycarbonyl-N-methylamino) propionylamino and 3- (N-tert-butoxycarbonyl-N-methylamino) propionylamino groups], N-alkoxycarbonyl-N-alkylamino substituted butyrylamino groups [such as 2- (N-methoxycarbonyl-N-methylamino) butyrylamino, 4- (N-methoxycarbonyl-N-methylamino) butyrylamino, 2- (N-ethoxycarbonyl-N-methylamino ) butyrylamino and 4- (N-ethoxycarbonyl-N-methylamino) butyrylamino groups], N-alkoxycarbonyl-N-alkylamino substituted isobutyrylamino groups [such as 2- (N-methoxycarbonyl-N-methylamino) -2-methylpropionylamino, 2- (N-ethoxycarbonyl -N-methylamino) -2-methylpropionylamino, 2- (N-propoxycarbonyl-N-methylamino) -2-methylpropionylamino, 2- (N-isopropoxycarbonyl-N-m tilamino) -2-methylpropionylamino, 2- (N-butoxycarbonyl-N-methylamino) -2-methylpropionylamino and 2- (N-tert-butoxycarbonyl-N-methylamino) -2-methylpropionylamino], N-alkoxycarbonyl-N-alkylamino substituted pentanoylamino [such as 5- (N-methoxycarbonyl-N-methylamino) pentanoylamino and 5- (N-ethoxycarbonyl-N-methylamino) pentanoylamino groups], N-alkoxycarbonyl-N-alkylamino substituted 4-methylpentanoylamino groups [such as 2- (N-methoxycarbonyl- N-methylamino) -4-methylpentanoylamino and 2- (N-ethoxycarbonyl-N-methylamino) -4-methylpentanoylamino], N-alkoc Icarbonyl-N-alkylamino-substituted isovalerylamino groups [such as 2- (N-methoxycarbonyl-N-methylamino) amino-3-methylbutyrylamino and 2 (N-ethoxycarbonyl-N-methylamino) -3-methylbutyrylamino groups], N alkoxycarbonyl-N-alkylamino-substituted amino-substituted such as 6- (N-methoxycarbonyl-N-methylamino) hexanoylamino group], N-alkoxycarbonyl-N-alkylamino substituted 3,3-dimethylbutyrylamino groups [such as 2- (N-methoxycarbonyl-N-methylamino) -3,3-dimethylbutyrylamino and 2 - (N-ethoxycarbonyl-N-methylamino) -3,3-dimethyl butyrylamino] and N-alkoxycarbonyl-N-al kilo-substituted heptanoylamino groups [such as 7- (N-methoxycarbonyl-N-methyl amino) aminoheptanoylamino group], of which N-alkoxycarbonyl-N-methylamino-substituted acetylamino, propionylamino and butyrylamino groups, in particular N-methoxymethylamino;
haloalkoxycarbonylamino substituted alkanoylamino groups in which the haloalkoxycarbonyl moiety has from 2 to 5 carbon atoms, the alkanoylamino moiety contains from 2 to 7 carbon atoms, and the halogen atom is preferably chlorine, bromine, fluorine or iodine, preferably chlorine or fluorine, in particular halogenaminoalkoxy acetylamino groups [such as chloromethoxycarbonylaminoacetylamino, trichloromethoxycarbonyl aminoacetylamino, 2,2,2-trifluoroethoxycarbonylaminoacetylamino, 3-bromopropoxycarbo ilaminoatsetilamino and 4 hlorbutoksikarbonil aminoatsetilaminogruppy] galogenalkoksikarbonilaminozameschennye propionylamino [such as 2-hlormetoksikarbonilamino propionylamino, 2-trihlormetoksikarbonilaminopropionilamino, hlormetoksikarbonilaminopropionilamino-3, 3-trihlormetoksikarbonilaminopropionilamino, 2- (2,2,2-triftoretoksikarbonilamino) propionylamino, 3- (2,2, 2-trifluoroethoxycarbonylamino) propionylamino, 2- (3-bromopropoxycarbonylamino) propionylamino, 3- (3-bromopropoxycarbonylamino) propionylamino, 2- (4-chlorobutoxycarbonyl mino) propionylamino and 3- (4-chlorobutoxycarbonylamino) propionylamino groups], haloalkoxycarbonylamino-substituted butyrylamino groups [such as 2-chloromethoxycarbonylaminobutyrylamino, 4-chloro-methoxycarbonylaminobutyrylamino, 2- (2,2,2-trifluoro-ethoxy-butoxy-butoxy) trifluoroethoxycarbonylamino) butyryl amino groups], haloalkoxycarbonylamino-substituted isobutyryl amino groups [such as 2-chloromethoxycarbonylamino-2-methylpropionylamino, 2- (2,2,2-trifluoroethoxycarbonylamino) -2-methylpropionylamino, 2- (3 amino) -2-metilpropionilamino and 2 (4- hlorbutoksikarbonilamino) -2-metilpropionilaminogruppy] galogenalkoksikarbonilaminozameschennye pentanoilaminogruppy [such as the 5- hlormetoksikarbonilaminopentanoilamino and 5- (2,2,2-trifluoroethoxy carbonylamino) pentanoilaminogruppy] galogenalkoksikarbonilamino substituted 4-metilpentanoilaminogruppy [such as 2-chloromethoxy carbonylamino-4-methylpentanoylamino and 2- (2,2,2-trifluoro-ethoxycarbonylamino) -4-methylpentanoylamino], haloalkoxycarbonyl amino-substituted isovalerylamino groups [such as 2 ormethoxycarbonylamino-3-methylbutyrylamino and 2- (2,2,2-trifluoroethoxycarbonylamino) -3-methylbutyrylamino groups], haloalkoxycarbonylamino-substituted hexanoylaminoamino [such as 6-chloromethoxycarbonylamino-3-methoxycarbonylamino-3-methoxycarbonylamino-3-methoxycarbonylamino-dimethyl-3-methoxycarbonylamino-dimethylamino-dimethyl-3-methoxy-aminomethoxy-3-alkoxy-dimethylamino-dimethylamino-dimethylamino-dimethylamino-dimethylamino-dimethylamino-dimethylamino-dimethylamino-dimethylamino 3-dimethylbutyrylamino- and 2- (2,2,2-trifluoroethoxycarbonylamino) -3,3-dimethylbutyrylamino groups] and haloalkoxycarbonylamino substituted heptanoylamino groups [such as 7-chloromethoxycarbonylaminoheptane oilaminogruppa], of which preferred galogenalkoksikarbonilaminozameschennym acetylamino, propionylamino, butyrylamino, isobutyrylamino, isovalerylamino, 4-methyl-pentanoylamino and 3,3-dimetilbutirilaminogruppam particularly hlormetoksikarbonilaminoatsetilamino, 2,2,2-trifluoroethoxycarbonyl aminoatsetilamino, hlormetoksikarbonilaminopropionilamino-2, 3-hlormetoksikarbonilaminopropionilamino 2 -chloromethoxycarbonyl aminobutyrylamino, 2-chloromethoxycarbonylamino-2-methylpropionylamino, 2-chloromethoxycarbonylamino-3-methylbutyryl Mino, 2-hlormetoksikarbonilamino-4-methyl-pentanoylamino 2-hlormetoksikarbonilamino-3,3-dimetilbutirilaminogruppam;
carbocyclic arylcarbonylamino substituted alkanoylamino groups in which the alkanoylamino group has from 2 to 7 carbon atoms and the aryl part contains from 6 to 10 carbon atoms in the ring (such aryl groups include phenyl, 1-naphthyl and 2-naphthyl), for example, benzoylaminoacetylamino, 3-benzoylaminoacetylamino amino 4-benzoyl aminobutyrylamino, 5-benzoylaminopentanoylamidino, 6-benzoylamino hexanoylamino, 7-benzoylaminoheptanoylamino and naphthoylaminoacetyl amino group;
aralkylcarbonylamino substituted alkanoylamino groups in which the alkanoylamino group has 2 to 7 carbon atoms, the aryl part is carbocyclic and has 6 to 10 carbon atoms in the ring, and the alkyl part contains 1 to 4 carbon atoms (such aralkyl groups include benzyl, phenethyl, 3- phenylpropionyl and 4-phenylbutyryl), for example, phenylacetylaminoacetylamino, 3-phenylpropionylaminoacetylamino, 4-phenylbutyrylaminoacetylamino and 5-phenylpentanoylaminoacetylamino;
carbocyclic aryl-substituted alkanoylamino groups in which the alkanoylamino group has from 2 to 7 carbon atoms and the aryl part contains from 6 to 10 carbon atoms in the ring, and they may be unsubstituted or substituted by at least one substituent selected from the group consisting of substituents γ, e.g. phenylacetylamino, 4-nitrophenylacetylamino, 4-fluorophenylacetylamino, 4-chlorophenylacetylamino, 4-methylphenylacetylamino, 4-ethylphenylacetylamino, 4-trifluoromethylphenylacetylamino, 4-aminomethylphenylacetylamino, 3-nitrophenylacetylamine 3-ftorfenilatsetilamino, 3-hlorfenilatsetilamino, 3- methylphenylacetylamino, 3-etilfenilatsetilamino, 3- triftormetilfenilatsetilamino, 3-aminometilfenilatsetilamino and 1- naftilatsetilaminogruppy;
alkanoylamino groups substituted with R ^h where R ^h represents a heterocyclic group with 3-6 atoms in the ring, of which at least one is a heteroatom selected from the group consisting of heteroatoms of nitrogen, oxygen and sulfur, said heterocyclic group being optionally substituted or substituted by at least one substituent selected from a group including γ substituents and oxygen atoms (to form an oxo group), for example, 2-oxo-1-azetidinylacetylamino, 2-oxo-1-piperidylacetylamino, 2,6-dioxo-1-piperidylacetylamino, pyrimidylacetylamino, pyridylacetylamino, 2 -oxo-1 - pyrrolidinylacetylamino, 2,5-dioxo-1-pyrrolidinylacetylamino, thiazolidinylacetylamino, thienylacetylamino, thiazolylacetylamino and 2-oxo-1,3-oxazolin-3-yl-acetylamino;
alkanoylamino groups substituted with a group of formula R ^h -S- where R ^h has the above meanings, for example, a 2-pyrimidylacetylamino, 2-pyridylacetylamino, 2-thiazolidinylacetylamino group;
alkanoylamino groups substituted by an alkanoyl group having 2-5 carbon atoms, e.g., atsetilatsetilamino, propionilatsetilamino, butirilatsetilamino, pivaloilatsetilamino, 3-atsetilpropionilamino, 3- propionilpropionilamino, 3-butirilpropionilamino, pivaloilpropionilamino 3, 4-atsetilbutirilamino, propionilbutiril 4-amino, 4-butirilbutirilamino and 4-pivaloyl butyrylamino groups;
and alkanoylamino groups substituted by aralkyloxycarbonylamino wherein the aryl part is carbocyclic and has from 6 to 10 ring carbon atoms and the alkyl part has from 1 to 4 carbon atoms, e.g., benziloksikarbonilaminoatsetilamino, fenetiloksikarbonilaminoatsetilamino, 3-fenilpropiloksikarbonil aminoatsetilamino, 4-fenilbutiloksikarbonilaminoatsetilamino and 5 phenylpentyloxycarbonylaminoacetylamino groups.

If R ³ represents a group of formula (iii), R ^{4 is a} cycloalkyl group with 3-6 carbon atoms, then this group is a cycloalkyl carbonylamino group. Examples of such groups include cyclopropane carbonylamino, cyclobutanecarbonylamino, cyclopentanecarbonylamino, cyclohexanecarbonylamino, N-methyl-N-cyclopropanecarbonylamino, N-methyl-N-cyclobutanecarbonylamino, N-methyl-N-methyl-N-cyclopentanecarbonylamino, N-methyl-N-methyl-N-methyl-N-methyl-N-methyl-N-cyclopentanecarbonylamino, N-cyclopropane carbonylamino, N-ethyl-N-cyclobutanecarbonylamino, N-ethyl-N-cyclopentanecarbonylamino, N-ethyl-N-cyclohexanecarbonylamino, N-propyl-N-cyclopropanecarbonylamino, N-propyl-N-cyclobutanecarbonylamino, -cyclopentanecarbonylamino and N-propyl-N-cyclohex ankarbonilaminogruppy.

If R ³ represents a group of formula (iii) and R ^{4 is a} cycloalkyl group with 3-10 carbon atoms which is substituted with at least one substituent selected from the group consisting of the above substituents β, the unsubstituted cycloalkyl group may be monocyclic or polycyclic, for example , a bicyclic ring system, in particular a cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, norbornyl, norkinanyl, boryl or mentyl group.

 Examples of a group of formula (iii) include 1-aminocyclobutane-1-carbonyl, 1-aminocyclopentane-1-carbonyl, 1-aminocyclohexane-1-carbonyl, 2-chlorocyclobutane-1-carbonyl, 2-chlorocyclopentane-1-carbonyl, 2-chloro cyclohexane-1-carbonyl, 2-fluorocyclobutane-1-carbonyl, 2-fluorocyclopentane-1-carbonyl, 2-fluorocyclohexane-1-carbonyl, 2-methoxycyclobutane-1-carbonyl, 2-methoxycyclopentane-1-carbonyl, 2-methoxycyclohexane- 1-carbonyl, 2-ethoxycyclobutane-1-carbonyl, 2-ethoxycyclopentane-1-carbonyl, 2-ethoxycyclohexane-1-carbonyl, 2-acetoxycyclobutane-1-carbonyl, 2-acetoxycyclopentane-1-k rbonil, 2-atsetoksitsiklogeksan-1- carbonyl, 2-propioniloksitsiklobutan-1-carbonyl, 2-propioniloksitsiklopentan-1-carbonyl and 2-propioniloksitsiklogeksan-1-carbonyl.

If R ³ represents a group of formula (iii) and R ^{4 is an} alkenyl group with 2-6 carbon atoms, the alkenyl group may have a straight or branched chain with 2-6, preferably 3 or 4 carbon atoms. Examples of such alkenyl groups include vinyl, allyl, metall, 1-propenyl, isopropenyl, 1-butenyl, 2-butenyl, 3-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl and 4-pentenyl, of which vinyl is preferred. allyl, metal, 1-propenyl, isopropenyl and butenyl groups. Preferred examples of the group of formula (iii) expressed by the symbol R ³ include acryloylamino, crotonoylamino, isocrotonoylamino, 3-butenoylamino, 2-pentenoylamino, 4-pentenoylamino, 2-hexenoylamino and 5-hexenoylamino, of which acrilonoylaminoaminoamino-amino-aminoamino is most preferred.

If R ³ represents a group of formula (iii) and R ^{4 is an} alkynyl group with 2-6 carbon atoms, the alkynyl group may have a straight or branched chain with 2-6, preferably 3 or 4 carbon atoms. Examples of such alkynyl groups include ethynyl, propargyl- (2-propynyl), 1-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl and 4-pentinyl, of which preference given to ethynyl, propynyl and butynyl groups. Preferred examples of the group of formula (iii) expressed by R ³ include propioloyl, 3-butynoylamino, 2-pentinoylamino, 4-pentinoylamino, 2-hexinoylamino and 5-hexinoylamino, of which the propioloyl group is most preferred.

If R ³ represents a group of formula (iii) and R ^{4 is a} carbocyclic aryl group with 6-14 carbon atoms in the ring, which may be unsubstituted or substituted by at least one substituent selected from the group consisting of the above substituents γ. Examples of groups of formula (iii) include benzoylamino, 1-naphthoylamino, 2-naphthoylamino, 1-fluorenecarbonylamino, 1-phenanthrenocarbonylamino, 1-anthracenecarbonylamino, 2-fluorobenzoylamino, 3-fluorobenzoylamino, 4-fluorobenzoylobenoyl-2-chloro-benzoylamino -chlorobenzoylamino, 2-methylbenzoylamino, 3-methylbenzoylamino, 4-methylbenzoylamino, 2-ethylbenzoylamino, 3-ethylbenzoylamino, 4-ethylbenzoylamino, 2-propylbenzoylamino-4-propylbenzoylamino-4-propylbenzoylamino-4-propylbenzoylamino-4-propylbenzoylamino 2-butylbene oylamino, 3-butylbenzoylamino, 4-butylbenzoylamino, 2-tert-butylbenzoylamino, 3-tert-butylbenzoylamino, 4-tert-butylbenzoylamino, 2-methoxybenzoylamino, 3-methoxybenzoylamino, 4-methoxybenzoamino 3 etoksibenzoilamino, 4-etoksibenzoilamino, 2-propoksibenzoilamino, 3-propoksibenzoilamino, 4-propoksibenzoilamino, 2-izopropoksibenzoilamino, 3-izopropoksibenzoilamino, 4-izopropoksibenzoilamino, 2-butoksibenzoilamino, 3-butoksibenzoilamino, 4-butoksibenzoilamino, 2-tert-butoksibenzoilamino, 3-tert- butoksibenzoilamino, 4-tert-butoksibenzoilamino, 2-nitrobenzoylamino, 3-nitrobenzoylamino, 4-nitrobenzoylamino, 2-aminobenzoylamino, 3-aminobenzoylamino and 4-aminobenzoilaminogruppy, of which preference is given benzoylamino, 2-fluorobenzoylamino, 3-fluorobenzoylamino, 4-fluorobenzoylamino, 3-chlorobenzoylamino, 4-chlorobenzoylamino, 3-methoxybenzoylamino, 4-methoxybenzoylamino, 3,4-dimethoxybenzoylamino, 4-tert-butylbenzoylamino, 3-nitrobenzoylamino and 4-nitrobenzoylamino.

If R ³ represents a group of formula (iii), and R ^{4 is a} heterocyclic group with 3-6 atoms in the ring, of which at least one is a heteroatom selected from the group consisting of nitrogen, oxygen and sulfur hetero atoms, then the heterocyclic group may not be substituted or substituted by at least one substituent selected from the group consisting of the above substituents γ and oxygen atoms (to form an oxo group). Examples of such heterocyclic groups are furyl, lactam, piperidyl, pyrimidyl, pyrrolidinyl, thiazolidinyl, thienyl and thiazolyl, which may or may not be substituted. Typical examples of the groups of formula (iii) include 2-furoylamino, 3-furoylamino, 5-γ-lactamcarbonylamino, 2-piperidine-carbonylamino, 3-piperidinecarbonylamino, 4-piperidinecarbonylamino, 1-methoxycarbonyl-4-piperidinecarbonylamino piperidinecarbonylamino, 2-pyrimidinecarbonylamino, 3-pyrimidinecarbonylamino, 3-pyridinecarbonylamino, 4-pyridinecarbonylamino, 3-pyrrolidinecarbonylamino, 1-methoxycarbonyl-2-pyrrolidinecarbonylamino, 1-eth-3-pyrrolidinecarbonylamino, 1-eth-3-pyrorolidinecarbonylamino arbonyl-4-thiazolidinecarbonylamino, 3-ethoxycarbonyl-4-thiazolidinecarbonylamino, 2-thienyl and 3-thienyl, of which 2-furoylamino, γ-amtamicarbonylamino, 1-methoxycarbonyl-4-piperidinecarbonylamino-4-piperidinecarbonylamino-4-piperidinylcarbonylamino-4-piperidinocarbonylamino-4-piperidinecarbonylamino-4-piperidinecarbonylamino-4-piperidinecarbonylamino-4-piperidinecarbonylamino-4-piperidinecarbonylamino , 1-methoxycarbonyl-2-pyrrolidininecarbonylamino, 1-ethoxycarbonyl-2-pyrrolidinecarbonylamino, 3-methoxycarbonyl-4-thiazolidinecarbonylamino and 2-thienyl groups.

If R ³ represents a group of formula (iii), (iv), (vii), (viii) or (ix), and R ^{5 is} an alkyl group, then this group may have a straight or branched chain with 1-4, preferably 1 or 2 carbon atoms. Examples of such groups are methyl, ethyl, propyl, isopropyl, butyl, isobutyl and tert-butyl. Of these, a methyl group is most preferred.

If R ³ represents a group of formula (iv) and R ^{6 is} an alkyl group, this group may have a straight or branched chain with 1-6, preferably 1-5 carbon atoms. Examples of such groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 2-methylbutyl, 1-ethylpropyl, 4 methylpentyl, 3-methylpentyl, 2-methylpentyl, 1- methylpentyl, 3,3-dimethylbutyl, 2,2-dimethylbutyl, 1,1-dimethylbutyl, 1,2-dimethylbutyl, 1,3-dimethylbutyl, 2,3-dimethylbutyl, 2-ethylbutyl, hexyl and isohexyl. Of these, preference is given to alkyl groups with 1-4 carbon atoms, in particular methyl, ethyl, propyl, isopropyl, butyl and isobutyl groups, and the methyl group is most preferred.

If R ³ represents a group of formula (iv) and R ^{6 is a} cycloalkyl group, then this group has from 3 to 6 carbon atoms. Examples of such groups are cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl groups.

If R ³ represents a group of formula (iv) and R ^{7 is} an alkyl or cycloalkyl group, then such groups may be any of the groups listed above for the symbol R ⁶ .

If R ³ represents a group of formula (iv) and R ^{7 is an} aryl group, then such a group is a carbocyclic aryl group with 6-14 carbon atoms in the ring, which may be unsubstituted or substituted by at least one substituent selected from the group consisting of γ substituents mentioned above. Examples of such aryl groups include phenyl, 1-naphthyl, 2-naphthyl, 1-fluorenyl, 1-phenanthrenyl, 1-anthracenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3- chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 2- ropylphenyl, 3-propylphenyl, 4-propylphenyl, 2-isopropylphenyl, 3-isopropylphenyl, 4-isopropylphenyl, 2-butylphenyl, 3-butylphenyl, 4-butylphenyl, 2-tert-butylphenyl, 3-tert-butylphenyl, 4-tert- butylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 2-propoxyphenyl, 3-propoxyphenyl, 4-propoxyphenyl, 2-isopropoxyphenyl, 3-isopropoxyphenyl, 4-isopropoxyphenyl, 3-butoxyphenyl, 3-butoxyphenyl, 4-butoxyphenyl, 2-tert-butoxyphenyl, 3-tert-butoxyphenyl, 4-tert-butoxyphenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl l, 2-aminophenyl, 3-aminophenyl and 4-aminophenyl, of which phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3 are most preferred. , 4-dimethoxyphenyl, 4-tert-butylphenyl, 3-nitrophenyl and 4-nitrophenyl.

If R ³ represents a group of formula (iv), and R ⁶ and R ⁷ together with the nitrogen atom to which they are attached form a heterocyclic ring with 3-6 atoms in the ring, then such groups can be any nitrogen-containing heterocyclic groups, examples of which are given above for the symbol R ⁴ , preferably a 1-pyrrolidinyl group.

If R ³ represents a group of formula (vii), (viii) or (ix) and R ^{8 is} an alkyl group, then it may have a straight or branched chain with 1 to 4, preferably 1 or 2 carbon atoms. Examples of such groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl and tert-butyl. Of these, a methyl group is most preferred.

If R ³ represents a group of formula (vii), (viii) or (ix) and R ^{8 is an} aryl group, then such a group is a carbocyclic aryl group with 6-10 carbon atoms in the ring, which may be unsubstituted or substituted at least one substituent selected from the group comprising the above substituents γ. Examples of such aryl groups include phenyl, 1-naphthyl, 2-naphthyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl , 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 2-propylphenyl, 3-propylphenyl, 4-propylphenyl, 2-isopropylphenyl, 3-isopropylphenyl, 4-isopropylphenyl, 2-butylphenyl, 3-butylphenyl, 4-butylphenyl, 2 tert-butylphenyl, 3-tert-butylphenyl, 4-tert-butylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 2-propoxyphenyl 3-propoxyphenyl, 4-propoc syphenyl, 2-isopropoxyphenyl, 3-isopropoxyphenyl, 4-isopropoxyphenyl, 2-butoxyphenyl, 3-butoxyphenyl, 4-butoxyphenyl, 2-tert-butoxyphenyl, 3-tert-butoxyphenyl, 4-tert-butoxyphenyl, 2-nitrophenyl, 3- nitrophenyl, 4-nitrophenyl, 2-aminophenyl, 3-aminophenyl and 4-aminophenyl, of which phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3-methoxyphenyl, 4 are most preferred -methoxyphenyl, 3,4-dimethoxyphenyl, 4-tert-butylphenyl, 3-nitrophenyl and 4-nitrophenyl.

If R ³ represents a group of formula (viii) and R ^{9 is} an alkyl or aryl group, then such a group may be any of the above groups, examples of which are given for the symbol R ⁸ .

If R ³ represents a group of formula (viii) and R ^{9 is a} cycloalkyl group, then such a group may be any of the above groups, examples of which are given for the symbol R ⁶ .

If R ³ represents a group of formula (viii) and R ⁹ represents an aralkyl group, then the aryl part is carbocyclic and has from 6 to 10 carbon atoms in the ring, and the alkyl part contains from 1 to 4 carbon atoms, the alkyl and aryl parts of this groups can be defined independently from each other and are given as examples for the symbol R ⁸ . Typical examples of such aralkyl groups include benzyl, 1-phenylethyl, 2-phenylethyl (phenyl), 3-phenylpropyl, 2-phenylpropyl, 4-phenylbutyl, 2-phenylbutyl, 1-naphthylmethyl and 2-naphthylmethyl. These groups may be unsubstituted or substituted, wherein the substituent or substituents, if used, are selected from the group consisting of the above substituents γ. Examples of substituted groups include 2-fluorobenzyl, 3-fluorobenzyl, 4-fluorobenzyl, 2-chlorobenzyl, 3-chlorobenzyl, 4-chlorobenzyl, 2-methylbenzyl, 3-methylbenzyl, 4-methylbenzyl, 2-ethylbenzyl, 3-ethylbenzyl, 4- ethylbenzyl, 2-propylbenzyl, 3-propylbenzyl, 4-propylbenzyl, 2-isopropylbenzyl, 3-isopropylbenzyl, 4-isopropylbenzyl, 2-butylbenzyl, 3-butylbenzyl, 4-butylbenzyl, 2-tert-butylbenzyl, 3-tert tert-butylbenzyl, 2-methoxybenzyl, 3-methoxybenzyl, 4-methoxybenzyl, 3,4-dimethoxybenzyl, 2-ethoxybenzyl, 3-ethoxybenzyl, 4-ethoxybenzyl, 2-propoxybenzyl, 3-propoxybenzyl, 4- propoxybenzyl, 2-isopropoxybenzyl, 3-isopropoxybenzyl, 4-isopropoxybenzyl, 2-butoxybenzyl, 3-butoxybenzyl, 4-butoxybenzyl, 2-tert-butoxybenzyl, 3-tert-butoxybenzyl, 4-tert-butoxybenzyl, 2-nitrobenzyl nitrobenzyl, 4-nitrobenzyl, 2-aminobenzyl, 3-aminobenzyl and 4-aminobenzyl.

If R ³ represents a group of formula (ix) and R ¹⁰ represents a heterocyclic group, then this group may be any of the heterocyclic groups exemplified for the above R ⁴ symbol, preferably 2-chloroacetylamino-4-thiazolyl, 2-methoxycarbonylamino -4-thiazolyl or 2-thienyl group.

If R ³ represents a group of formula (ix) and R ¹ represents an alkyl group, then such a group may have a straight or branched chain with 1-3 carbon atoms, examples of which are methyl, ethyl, propyl and isopropyl. Of these, methyl group is preferred.

Substituents α include:
halogen atoms, in particular fluorine, chlorine, bromine or iodine atoms, of which fluorine and chlorine atoms are most preferred;
cyano groups;
alkoxy groups of 1-4 carbon atoms, in particular methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy and tert-butoxy, of which the methoxy group is most preferred;
alkylthio groups with 1-4 carbon atoms, in particular methylthio, ethylthio, propylthio, isopropylthio, butylthio, isobutylthio, sec-butylthio and tert-butylthio, of which methylthio is most preferred;
alkylsulfonyl groups with 1-4 carbon atoms, in particular methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, butylsulfonyl, isobutylsulfonyl, sec-butylsulfonyl and tert-butylsulfonyl, of which the methylsulfonyl group is most preferred;
alkanoyloxy groups with 2-5 carbon atoms, in particular acetoxy, propionyloxy, butyryloxy, isobutyryloxy, valeryloxy, isovaleryloxy and pivaloyloxy, of which the acetoxy group is most preferred;
alkoxycarbonyl groups with 2-5 carbon atoms, in particular methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl and tert-butoxycarbonyl, of which the methoxycarbonyl group is most preferred;
carbocyclic aryloxy groups with 6 to 10 carbon atoms in the ring, in particular phenoxy, 1-naphthyloxy and 2-naphthyloxy, of which the phenoxy group is most preferred;
carbocyclic arylthio groups with 6-10 carbon atoms in the ring, in particular phenylthio, 1-naphthylthio and 2-naphthylthio, of which phenylthio is most preferred;
carbocyclic arylsulfonyl groups with 6 to 10 ring carbon atoms, in particular phenylsulfonyl, 1-naphthylsulfonyl and 2-naphthylsulfonyl, of which the phenylsulfonyl group is most preferred;
amino groups;
alkanoylamino groups with 2-5 carbon atoms, in particular acetylamino, propionylamino, butyrylamino, isobutyrylamino, valerylamino, isovalerylamino and pivaloylamino, of which the acetylamino group is most preferred;
N- (C ₂ -C ₅ alkanoyl) -N- (C ₁ -C ₃ alkyl) amino groups, in particular N-acetyl-N-methylamino, N-propionyl-N-methylamino, N-butyryl-N-methylamino, N -isobutyryl-N-methylamino, N-valeryl-N-methylamino, N-isovaleryl-N-methipamino, N-pivaloyl-N-methylamino, N-acetyl-N-ethylamino, N-propionyl-N-ethylamino, N-butyryl - N-ethylamino, N-isobutyryl-N-ethylamino, N-valeryl-N-ethylamino, N-isovaleryl-N-ethylamino, N-pivaloyl-N-ethylamino, N-acetyl-N-propylamino, N-propionyl-Npropylamino , N-butyryl-N-propylamino, N-isobutyryl-N-propylamino, N-valeryl-N-propylamino, N-isovaleryl-N-propylamino, N-pivaloyl-N-propi amino, N-acetyl-N-isopropylamino, N-propionyl-N-isopropylamino, N-butyryl-N-isopropylamino, N-isobutyryl-N-isopropylamino, N-valeryl-N-isopropylamino, N-isovaleryl-N-isopropylamino and N-pivaloyl-N-isopropylamino, of which the most preferred is N-methyl-N-acetylamino;
haloalkanoylamino groups with 2-5 carbon atoms, in particular chloroacetylamino, dichloroacetylamino, trichloroacetylamino, fluoroacetylamino, difluoroacetylamino, trifluoroacetylamino, bromoacetylamino, iodoacetylamino, 4-chlorobutylamino, 4-fluoro-butylamino-preferred, 4-fluoro-butylamino
alkoxycarbonylamino groups with 2-5 carbon atoms, in particular methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, isopropoxycarbonylamino, butoxycarbonylamino, isobutoxycarbonylamino, sec-butoxycarbonylamino and tert-butoxycarbonylamino, of which the most preferred is;
N- (C ₂ -C ₅ alkoxycarbonyl) -N- (C ₁ -C ₃ alkyl) amino groups, in particular N-methoxycarbonyl-N-methylamino, N-ethoxycarbonyl-N-methylamino, N-propoxycarbonyl-N-methylamino, N -isopropoxycarbonyl-N methylamino, N-butoxycarbonyl-N-methylamino, N-isobutoxycarbonyl-N-methylamino, N-sec-butoxycarbonyl-N-methylamino, N-tert-butoxycarbonyl-N-methylamino, N-methoxycarbonyl-N-ethylamino , N-ethoxycarbonyl-N-ethylamino, N-propoxycarbonyl-N-ethylamino, N-isopropoxycarbonyl-N-ethylamino, N-butoxycarbonyl-N-ethylamino, N-isobutoxycarbonyl-N-ethylamino, N-sec-butoxycarbonyl-N-ethyl mino, N-tert-butoxycarbonyl-N-ethylamino, N-methoxycarbonyl-N-propylamino, N-ethoxycarbonyl-N-propylamino, N-propoxycarbonyl-N-propylamino, N-isopropoxycarbonyl-N-propylamino, N-butoxycarbonyl-N- propylamino, N-isobutoxycarbonyl-N-propylamino, N-sec-butoxycarbonyl-N-propylamino, N-tert-butoxycarbonyl-N-propylamino, N-methoxycarbonyl-N-isopropylamino, N-ethoxycarbonyl-N-isopropylamino, N-propoxycarbonyl N-isopropylamino, N-isopropoxycarbonyl-N-isopropylamino, N-butoxycarbonyl-N-isopropylamino, N-isobutoxycarbonyl-N-isopropylamino, N-sec. oxycarbonyl-N-isopropylamino and N-tert-butoxycarbonyl-N- isopropylamino, of which the most preferred is N-methoxycarbonyl-N-methylamino;
haloalkoxycarbonylamino with 2-5 carbon atoms, in particular hlormetoksikarbonilamino, dihlormetoksikarbonilamino, trihlormetoksikarbonilamino, ftormetoksikarbonilamino, diftormetoksikarbonilamino, triftormetoksikarbonilamino, ftormetoksikarbonilamino, diftormetoksikarbonilamino, triftormetoksikarbonilamino, brommetoksikarbonilamino, iodmetoksikarbonilamino, 2-chloroethoxycarbonylamino, 2-ftoretoksikarbonilamino, brometoksikarbonilamino-2, 2-iodetoksikarbonilamino, 2, 2,2-trifluoroethoxycarbonylamino, 2,2,2-trichloroethoxy arbonylamino, 3-fluoropropoxycarbonylamino, 3-chloropropoxycarbonylamino, 3-bromopropoxycarbonylamino, 3-iodopropoxycarbonylamino, 4-chlorobutoxycarbonylamino and 5-chloropentyloxycarbonylamino, of which chloromethoxycarbonylamino and 2,2 are most preferred;
carbocyclic arylcarbonylamino groups in which the aryl part has from 6 to 10 carbon atoms in the ring, in particular benzoylamino, 1-naphthoylamino and 2-naphthoylamino, of which the benzoylamino group is most preferred;
aralkylcarbonylamino groups in which the aryl part is carbocyclic and contains from 6 to 10 carbon atoms in the ring and the alkyl part has from 1 to 4 carbon atoms, in particular phenylacetylamino, 2-phenylpropionylamino, 3-phenylpropionylamino, 4-phenylbutyrylamino, 3-phenylbutylamino 4-phenylvalerylamino, 2-phenylvalerylamino, 1-naphthylacetylamino and 2-naphthylacetylamino, of which phenylacetylamino is most preferred;
carbocyclic aryl groups with 6-10 carbon atoms in the ring that may be unsubstituted or substituted by at least one substituent selected from the group consisting of substituents such as phenyl, 1-naphthyl, 2-naphthyl, 2-fluorophenyl, 3- fluorophenyl, 4-fluorophenyl, 2-chlorophenyl, 3-chlorophenyl, 4-chlorophenyl, 2-methylphenyl, 3-methylphenyl, 4-methylphenyl, 2-ethylphenyl, 3-ethylphenyl, 4-ethylphenyl, 2-propylphenyl, 3-propylphenyl, 4-propylphenyl, 2-isopropylphenyl, 3-isopropylphenyl, 4-isopropylphenyl, 2-butylphenyl, 3-butylphenyl, 4-butylphenyl, 2-tert-butylphenyl, 3-tert-butylphenyl, 4-t ret-butylphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 3,4-dimethoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 2-propoxyphenyl, 3-propoxyphenyl, 4-propoxyphenyl, 2-isopropoxyphenyl, 3-isopropoxyphenyl, 4-isopropoxyphenyl, 2-butoxyphenyl, 3-butoxyphenyl, 4-butoxyphenyl, 2-tert-butoxyphenyl, 3-tert-butoxyphenyl, 4-tert-butoxyphenyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 2- aminophenyl, 3-aminophenyl and 4-aminophenyl, of which phenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 3-chlorophenyl, 4-chlorophenyl, 3-methoxyphenyl are most preferred 4-methoxyphenyl, 3,3-dimethoxyphenyl, 4-tert-butylphenyl, 3-nitrophenyl and 4-nitrophenyl;
groups R ^h , where R ^g represents a heterocyclic group with 3-6 atoms in the ring, of which at least one is a heteroatom of nitrogen, oxygen or sulfur, and the specified heterocyclic group may be unsubstituted or substituted by at least one substituent selected from a group consisting of γ substituents and oxygen atoms (to form an oxo group), in particular 2-oxo-1-azetidinyl, 2-oxo-1-piperidyl, 2,6-dioxo-1-piperidyl, pyrimidyl, pyridyl, 2-oxo 1-pyrrolidinyl, 2,5-dioxo-1-pyrrolidinyl, thiazolidinyl, thienyl, thiazolyl and 2-oxo-1,3- oxazolyl-3-yl;
groups of the formula R ^h —S—, where R ^h has the above meanings, in particular 2-oxo-1-azetidinylthio, 2-oxo-1-piperidylthio, 2,6-dioxo-1-piperidylthio, pyrimidylthio, pyridylthio, 2- oxo-1-pyrrolidinylthio, 2,5-dioxo-1-pyrrolidinylthio, thiazolidinylthio, thienylthio, thiazolylthio and 2-oxo-1,3-oxazolin-3-ylthio, of which 2-pyrimidylthio, 2-pyridylthio and 2 are most preferred thiazolidinylthio groups;
alkanoyl groups with 2-5 carbon atoms, in particular acetyl, propionyl, butyryl, isobutyryl, valeryl, isovaleryl and pivaloyl, of which the acetyl group is most preferred;
aralkyloxycarbonylamino groups in which the aryl part is carbocyclic and contains from 6 to 10 carbon atoms in the ring and the alkyl part has from 1 to 4 carbon atoms, in particular benzyloxycarbonylamino, phenyloxycarbonylamino, 3-phenylpropyl hydroxycarbonylamino, 4-phenylbutyloxycarbonylaminoamino and 5-phenylbutyloxycarbonylamino.

Examples of groups that may be included in the number of substituents β are:
halogen atoms, in particular fluorine, chlorine, bromine or iodine atoms, of which fluorine and chlorine atoms are most preferred;
alkoxy groups with 1-4 carbon atoms, in particular methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy and tert-butoxy, of which the methoxy group is most preferred; and
alkanoyloxy groups with 2-5 carbon atoms, in particular acetoxy, propionyloxy, butyryloxy, isobutyryloxy, valeryloxy, isovaleryloxy and pivaloyloxy, of which acetoxy is most preferred.

Examples of groups that may be included in the number of substituents γ are:
halogen atoms, in particular fluorine, chlorine, bromine or iodine atoms, of which fluorine and chlorine atoms are most preferred;
hydroxyl groups;
cyano groups;
nitro groups;
alkyl groups with 1-4 carbon atoms, in particular methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl and tert-butyl, of which the methyl group is most preferred;
alkoxy groups with 1-4 carbon atoms, in particular methoxy, ethoxy, propoxy, isopropoxy, butoxy, isobutoxy, sec-butoxy and tert-butoxy, of which the methoxy group is most preferred;
and alkoxycarbonyl groups containing a total of 2 to 5 carbon atoms (i.e., the alkoxy part has 1 to 4 carbon atoms), in particular methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, isobutoxycarbonyl, sec-butoxycarbonyl and tert-butoxycarbonyl, of which the methoxycarbonyl group is most preferred.

Examples of groups which may be included in the number of substituents δ, are:
amino groups;
alkanoylamino groups with 2-5 carbon atoms, in particular acetylamino, propionylamino, butyrylamino, isobutyrylamino, valerylamino, isovalerylamino and pivaloylamino, of which the acetylamino group is most preferred;
haloalkanoylamino groups with 2-5 carbon atoms, in particular chloroacetylamino, dichloroacetylamino, trichloroacetylamino, fluoroacetylamino, difluoroacetylamino, trifluoroacetylamino, bromoacetylamino, iodoacetylamino, 4-chlorobutylamino, 4-fluoro-amino-fluoro-butylamino-acetylamino, and
alkoxycarbonylamino groups having from 2 to 6 carbon atoms, in particular methoxycarbonylamino, ethoxycarbonylamino, propoxycarbonylamino, isopropoxycarbonylamino, butoxycarbonylamino, isobutoxycarbonylamino, sec-butoxycarbonylamino, tert-butoxycarbonylamino and pentyloxycarbonylmethyl is most preferred.

 As a rule, when it comes to substituents, there are no restrictions on the number of substituents, except for those related to the number of substitutable positions and the steric structure. However, if the group is substituted, then the number of substituents should be from 1 to 3, and it is preferable that the substituents be 0, 1 or 2, and even more preferably 0 or 1.

 The compounds of the present invention may have several asymmetric carbon atoms in the molecule and thus form optical isomers. Although all of these compounds are represented by the same molecular formula, the present invention includes both individual, isolated isomers, and mixtures thereof, including racemates.

 If stereospecific synthesis methods are used or optically active compounds are used as starting materials, individual isomers can be obtained as a result of direct interaction; on the other hand, if a mixture of isomers is obtained, then individual isomers can be obtained using conventional separation methods. In particular, the compounds of the present invention may exist as an α or β configuration with respect to the stereochemistry of position 13 of the milbemycin skeleton. Although all of these isomers and mixtures thereof are included in the scope of the present invention, β-configuration is preferred.

Preferred compounds of the present invention are those compounds of formula (I) in which
(A). Z is a group of formula (i) and R ^{2 is a} methyl or ethyl group; or
(A '). Z is a group of formula (iii), and m is 2, 3 or 4.

 (B), n is 0.

в которых R⁴ алкильная группа с 1-4 атомами углерода, замещенная алкильная группа с 1-3 атомами углерода, которая замещена по крайней мере одним заместителем, выбираемым из группы, включающей приводимые ниже заместители α¹, циклоалкильная группа с 3-6 атомами углерода, алкенильная группа с 3 или 4 атомами углерода, алкинильная группа с 3 или 4 атомами углерода, карбоциклическая арильная группа с 6-10 атомами углерода в кольце, которая может быть не замещена или замещена по крайней мере одним заместителем, отбираемым из группы, включающей приводимые ниже заместители γ¹, или гетероциклическая группа с 3-6 атомами в кольце, из которых по крайней мере один является гетероатомом, выбираемым из группы, включающей гетероатомы азота, кислорода и серы, причем указанная гетероциклическая группа может быть не замещена или замещена по крайней мере одним заместителем, выбираемым из группы, включающей приводимые ниже заместители

или атомы кислорода;
R⁵ - атом водорода или алкильная группа с 1-3 атомами углерода;
R⁶ - атом водорода или алкильная группа с 1-4 атомами углерода;
R⁷ - алкильная группа с 1-6 атомами углерода, карбоциклическая арильная группа с 6-10 атомами углерода в кольце, которая может быть не замещена или замещена по крайней мере одним заместителем, выбираемым из группы, включающей приводимые ниже заместители γ¹, или аралкильная группа, в которой арильная часть является карбоциклической и содержит от 6 до 10 атомов углерода в кольце, а алкильная часть имеет 1 или 2 атома углерода;
или
R⁶ и R⁷ вместе с атомом азота, в которому они присоединены, образуют гетероциклическое кольцо с 5 или 6 атомами в кольце;
Y атом кислорода или атом серы;
r означает 1, 2 или 3;
Q - метиленовая или карбонильная группа;
R⁸ - алкильная группа с 1-4 атомами углерода или карбоциклическая арильная группа с 6-10 атомами углерода, которая может быть не замещена или замещена по крайней мере одним заместителем, выбираемым из группы, включающей приводимые ниже заместители γ¹;
заместители α¹ выбирают из группы, включающей атомы галогенов, цианогруппы, алкоксильные группы с 1-3 атомами углерода, алкилтиогруппы с 1-3 атомами углерода, алканоилоксигруппы с 2-5 атомами углерода, алкоксикарбонильные группы с 2-4 атомами углерода, карбоциклические арилоксигруппы с 6-10 атомами углерода в кольце, карбоциклические арилтиогруппы с 6-10 атомами углерода в кольце, аминогруппы, алканоиламиногруппы с 2-5 атомами углерода, N-(C₂-C₅ алканоил)-N-(C₁-C₃ алкил)аминогруппы, галогеналканоиламиногруппы с 2-4 атомами углерода, алкоксикарбониламиногруппы с 2-4 атомами углерода, N-(C₂-C₅ алкоксикарбонил)-N-(C₁-C₃ алкил)аминогруппы, галогеналкоксикарбониламиногруппы с 2-5 атомами углерода; карбоциклические арилкарбониламиногруппы, в которых арильная часть имеет от 6 до 10 атомов углерода в кольце, аралкилкарбониламиногруппы, в которых арильная часть является карбоциклической и содержит от 6 до 10 атомов углерода в кольце, а алкильная часть имеет 1 или 2 атома углерода; карбоциклические арильные группы с 6-10 атомами углерода в кольце, которые могут быть не замещены или замещены по крайней мере одним заместителем, выбираемым из группы, включающей заместители γ¹, группы R^h, где R^h представляет гетероциклическую группу с 3-6 атомами в кольце, из которых по крайней мере один является гетероатомом, выбираемым из группы, включающей гетероатомы азота, кислорода и серы, причем указанная гетероциклическая группа может быть не замещена или замещена по крайней мере одним заместителем, выбираемым из группы, включающей приводимые ниже заместители γ¹ и атомы кислорода, группы формулы R^h-S-, где R^h имеет указанные выше значения, и алканоильные группы с 2-5 атомами углерода;
заместители γ¹ выбирают из группы, включающей атомы галогенов, цианогруппы, нитрогруппы, алкильные группы с 1-4 атомами углерода, алкоксильные группы с 1-4 атомами углерода и алкоксикарбонильные группы с 2-5 атомами углерода.(WITH). R ³ amino group, (C ₁ -C ₃ alkyl) amino group, di (C ₁ -C ₃ alkyl) amino group, alkoxyl group with 1-3 carbon atoms or a group of formula (iii), (iv), (v), (vi ) or (vii):

in which R ^{4 is an} alkyl group with 1-4 carbon atoms, a substituted alkyl group with 1-3 carbon atoms, which is substituted by at least one substituent selected from the group consisting of substituents α ¹ listed below, a cycloalkyl group with 3-6 carbon atoms , an alkenyl group with 3 or 4 carbon atoms, an alkynyl group with 3 or 4 carbon atoms, a carbocyclic aryl group with 6-10 carbon atoms in the ring, which may be unsubstituted or substituted by at least one substituent selected from the group consisting of f below the substituents γ ¹ , or a heterocyclic group with 3-6 atoms in the ring, of which at least one is a heteroatom selected from the group consisting of nitrogen, oxygen and sulfur heteroatoms, wherein said heterocyclic group may be unsubstituted or substituted at least at least one substituent selected from the group consisting of the following substituents

or oxygen atoms;
R ⁵ is a hydrogen atom or an alkyl group with 1-3 carbon atoms;
R ⁶ is a hydrogen atom or an alkyl group with 1-4 carbon atoms;
R ⁷ is an alkyl group with 1-6 carbon atoms, a carbocyclic aryl group with 6-10 carbon atoms in the ring, which may be unsubstituted or substituted by at least one substituent selected from the group consisting of the substituents γ ¹ given below, or aralkyl a group in which the aryl part is carbocyclic and contains from 6 to 10 carbon atoms in the ring, and the alkyl part has 1 or 2 carbon atoms;
or
R ⁶ and R ⁷ together with the nitrogen atom to which they are attached form a heterocyclic ring with 5 or 6 atoms in the ring;
Y is an oxygen atom or a sulfur atom;
r is 1, 2 or 3;
Q is a methylene or carbonyl group;
R ⁸ is an alkyl group with 1-4 carbon atoms or a carbocyclic aryl group with 6-10 carbon atoms, which may be unsubstituted or substituted by at least one substituent selected from the group consisting of the following substituents γ ¹ ;
substituents α ¹ are selected from the group consisting of halogen atoms, cyano groups, alkoxy groups with 1-3 carbon atoms, alkylthio groups with 1-3 carbon atoms, alkanoyloxy groups with 2-5 carbon atoms, alkoxycarbonyl groups with 2-4 carbon atoms, carbocyclic aryloxy groups with 6-10 carbon atoms in the ring, carbocyclic arylthio groups with 6-10 carbon atoms in the ring, amino groups, alkanoylamino groups with 2-5 carbon atoms, N- (C ₂ -C ₅ alkanoyl) -N- (C ₁ -C ₃ alkyl) amino groups, haloalkanoylamino groups with 2-4 carbon atoms, alkoxycarbonyls nogruppy with 2-4 carbon atoms, N- (C ₂ -C ₅ alkoxycarbonyl) -N- (C ₁ -C ₃ alkyl) amino, haloalkoxycarbonylamino with 2-5 carbon atoms; carbocyclic arylcarbonylamino groups in which the aryl part has 6 to 10 carbon atoms in the ring, aralkylcarbonylamino groups in which the aryl part is carbocyclic and contains 6 to 10 carbon atoms in the ring, and the alkyl part has 1 or 2 carbon atoms; carbocyclic aryl groups with 6-10 carbon atoms in the ring that may be unsubstituted or substituted by at least one substituent selected from the group consisting of γ ¹ substituents, R ^h groups, where R ^h represents a heterocyclic group with 3-6 atoms per a ring of which at least one is a heteroatom selected from the group consisting of nitrogen, oxygen and sulfur heteroatoms, said heterocyclic group being optionally substituted or substituted by at least one substituent selected from the group consisting of The following substituents γ ^1, and oxygen atoms, groups of formula R ^h -S-, where R ^h is as defined above, and alkanoyl groups having 2-5 carbon atoms;
substituents γ ¹ are selected from the group consisting of halogen atoms, cyano groups, nitro groups, alkyl groups with 1-4 carbon atoms, alkoxy groups with 1-4 carbon atoms and alkoxycarbonyl groups with 2-5 carbon atoms.

Of these compounds, compounds of formula (I) and their salts are most preferred, in which Z has the meanings indicated above in (A) or (A '), and R ³ has the meanings given above (C), and especially those in which Z has the meanings indicated in (A) or (A ') above, R ³ has the meanings given in (C) above, and n has the meanings specified in (B).

The most preferred compounds of the present invention are compounds of formula (I) in which:
(D) R ¹ is a methyl or ethyl group.

(E). Z is a group of formula (i) and R ^{2 is a} methyl group.

 (E '). Z is a group of formula (ii), and m is 2 or 4.

в которых R⁴ - алкильная группа с 1-4 атомами углерода, замещенная алкильная группа с 1-3 атомами углерода, которая замещена по крайней мере одним заместителем, выбираемым из группы, включающей приведенные ниже заместители α², циклоалкильная группа с 3-6 атомами углерода, алкенильная группа с 3 или 4 атомами углерода, алкинильная группа с 3 или 4 атомами углерода, карбоциклическая арильная группа с 6-10 атомами углерода, которая может быть не замещена или замещена по крайней мере одним заместителям, выбираемым из группы, включающей приведенные ниже заместители γ¹, или гетероциклическая группа с 3-6 атомами в кольце, из которых по крайней мере один является гетероатомом, выбираемым из группы, включающей гетероатомы азота, кислорода и серы, причем указанная гетероциклическая группа может быть не замещена или замещена по крайней мере одним заместителем, выбираемым из группы, включающей приведенные ниже заместители γ¹ и атомы кислорода;
r означает 1, 2 или 3;
Q - метиленовая или карбонильная группа;
заместители α² выбирают из группы, включающей атомы галогенов, цианогруппы, метоксильные группы, этоксильные группы, метилтиогруппы, этилтиогруппы, алканоилоксигруппы с 2 или 3 атомами углерода, алкоксикарбонильные группы с 2 или 3 атомами углерода, феноксильные группы, фенилтиогруппы, аминогруппы, алканоиламиногруппы с 2-5 атомами углерода, N-(C₂-C₅ алканоил)-N-(C₁-C₃ алкил)аминогруппы, галогеналканоиламиногруппы с 2-4 атомами углерода, алкоксикарбониламиногруппы с 2-4 атомами углерода, N-(C₂-C₅ алкоксикарбонил)-N-(C₁-C₃ алкил)аминогруппы, галогеналкоксикарбониламиногруппы с 2-5 атомами углерода, карбоциклические арилкарбониламиногруппы, в которых арильная часть имеет от 6 до 10 атомов углерода, аралкилкарбониламиногруппы, в которых арильная часть является карбоциклической и содержит от 6 до 10 атомов углерода в кольце, а алкильная часть имеет 1 или 2 атома углерода; фенильные группы, которые могут быть не замещены или замещены по крайней мере одним заместителем, выбираемым из группы, включающей заместители γ², группы R^h, где R^h представляет гетероциклическую группу с 3-6 атомами в кольце, из которых по крайней мере один является гетероатомом, выбираемым из группы, включающей гетероатомы азота, кислорода и серы, причем указанная гетероциклическая группа может быть не замещена или замещена по крайней мере одним заместителем, выбираемым из группы, включающей приводимые ниже заместители γ² и атомы кислорода, и группы формулы R^h-S-, где R^h имеют указанные выше значения;
заместители γ² выбирают из группы, включающей атомы галогенов, цианогруппы, нитрогруппы, метильные группы, этильные группы, метоксильные группы и алкоксикарбонильные группы с 2 или 3 атомами углерода.(F). R ³ amino group, methylamino group, ethylamino group, alkoxyl group with 1-3 carbon atoms or a group of the formula (iii), (v), (vi):

in which R ⁴ is an alkyl group with 1-4 carbon atoms, a substituted alkyl group with 1-3 carbon atoms, which is substituted by at least one substituent selected from the group consisting of substituents α ² listed below, a cycloalkyl group with 3-6 atoms carbon, alkenyl group with 3 or 4 carbon atoms, alkynyl group with 3 or 4 carbon atoms, carbocyclic aryl group with 6-10 carbon atoms, which may be unsubstituted or substituted by at least one substituent selected from the group consisting of the following substituents γ ^1, or a heterocyclic group having 3-6 ring atoms, of which at least one is a heteroatom selected from the group consisting of the heteroatoms nitrogen, oxygen and sulfur, said heterocyclic group may be unsubstituted or substituted by at least one a substituent selected from the group consisting of the following substituents γ ¹ and oxygen atoms;
r is 1, 2 or 3;
Q is a methylene or carbonyl group;
substituents α ² are selected from the group consisting of halogen atoms, cyano groups, methoxy groups, ethoxy groups, methylthio groups, ethylthio groups, alkanoyloxy groups with 2 or 3 carbon atoms, alkoxycarbonyl groups with 2 or 3 carbon atoms, phenoxy groups, phenylthio groups, amino groups, alkanoylamino groups with 2 -5 carbon atoms, N- (C ₂ -C ₅ alkanoyl) -N- (C ₁ -C ₃ alkyl) amino groups, haloalkanoylamino groups with 2-4 carbon atoms, alkoxycarbonylamino groups with 2-4 carbon atoms, N- (C ₂ - C ₅ alkoxycarbonyl) -N- (C ₁ -C ₃ alkyl) amino, halogen hydroxycarbonylamino groups with 2-5 carbon atoms, carbocyclic arylcarbonylamino groups in which the aryl part has 6 to 10 carbon atoms, aralkylcarbonylamino groups in which the aryl part is carbocyclic and contains 6 to 10 carbon atoms in the ring, and the alkyl part has 1 or 2 atoms carbon; phenyl groups which may be unsubstituted or substituted by at least one substituent selected from the group consisting of γ ² substituents, R ^h groups, where R ^h represents a heterocyclic group with 3-6 atoms in the ring, of which at least one is heteroatom selected from the group consisting of nitrogen heteroatoms, oxygen and sulfur, said heterocyclic group may be unsubstituted or substituted by at least one substituent selected from the group consisting of the substituents given below γ ² and the atoms kislor yes, and groups of formula R ^h -S-, where R ^h are as defined above;
γ ² substituents are selected from the group consisting of halogen atoms, cyano groups, nitro groups, methyl groups, ethyl groups, methoxy groups and alkoxycarbonyl groups with 2 or 3 carbon atoms.

Of these compounds, the compounds of formula (I) and their salts are most preferred, in which R ¹ has the meanings indicated above in (D), Z has the meanings indicated above in (E) or (E '), and R ³ has the meanings indicated in (F) above, especially compounds in which R ¹ has the meanings given in (D) above, Z has the meanings given in (E) or (E ') above, R ³ has the meanings above in paragraph (F), and n has the meanings given above in paragraph (B).

Even more preferred compounds of the present invention are those compounds of formula (I) in which
(G). R ¹ is an ethyl group.

в которых R⁴ - алкильная группа с 1-4 атомами углерода, замещенная алкильная группа с 1-3 атомами углерода, которая замещена по крайней мере одним заместителем, выбираемым из группы, включающей приведенные ниже заместители α³, циклоалкильная группа с 5 или 6 атомами углерода, фенильная группа, которая может быть не замещена или замещена по крайней мере одним заместителем, выбираемым из группы, включающей приведенные ниже заместители γ³, или гетероциклическая группа с 5 или 6 атомами в кольце, из которых по крайней мере один является гетероатомом, выбираемым из группы, включающей гетероатомы азота, кислорода и серы, причем указанная гетероциклическая группа может быть не замещена или замещена по крайней мере одним заместителем, выбираемым из группы, включающей приведенные ниже заместители γ³;
r означает 2;
Q - метиленовая или карбонильная группа;
заместители α³ выбирают из группы, включающей атомы галогенов, цианогруппы, метоксильные группы, этоксильные группы, алканоилоксигруппы с 2 или 3 атомами углерода, алкоксикарбонильные группы с 2 или 3 атомами углерода, феноксильные группы, аминогруппы, алканоиламиногруппы с 2 или 3 атомами углерода, алкоксикарбониламиногруппы с 2-4 атомами углерода и бензоилкарбониламиногруппы;
заместители

выбирают из группы, включающей атомы галогенов, цианогруппы, нитрогруппы, метильные группы, этильные группы, метоксильные группы и этоксильные группы.(H). R ³ is an amino group, methylamino group, ethylamino group or a group of the formula (iii) or (vi):

in which R ⁴ is an alkyl group with 1-4 carbon atoms, a substituted alkyl group with 1-3 carbon atoms, which is substituted by at least one substituent selected from the group consisting of substituents α ³ listed below, a cycloalkyl group with 5 or 6 atoms carbon, a phenyl group which may be unsubstituted or substituted by at least one substituent selected from the group consisting of γ ³ substituents listed below, or a heterocyclic group with 5 or 6 atoms in the ring, of which at least one is heteroatom m selected from the group consisting of nitrogen, oxygen and sulfur hetero atoms, said heterocyclic group being optionally substituted or substituted by at least one substituent selected from the group consisting of γ ³ substituents listed below;
r is 2;
Q is a methylene or carbonyl group;
substituents α ³ are selected from the group consisting of halogen atoms, cyano groups, methoxy groups, ethoxy groups, alkanoyloxy groups with 2 or 3 carbon atoms, alkoxycarbonyl groups with 2 or 3 carbon atoms, phenoxy groups, amino groups, alkanoylamino groups with 2 or 3 carbon atoms, alkoxycarbonylamino groups with 2-4 carbon atoms and a benzoylcarbonylamino group;
alternates

selected from the group consisting of halogen atoms, cyano groups, nitro groups, methyl groups, ethyl groups, methoxy groups and ethoxyl groups.

Of these compounds, compounds of formula (I) and salts thereof are preferred in which R ¹ has the meanings given above in (G), Z has the meanings specified in (E) or (E ') above, and R ³ has the meanings indicated in paragraph (H) above; particularly preferred are those compounds in which R ¹ has the meanings given above in (G), Z has the meanings given above in (E) or (E '), R ³ has the meanings given above in (H) , and n has the meanings given in (B) above.

в которой заместители имеют значения, указанные в таблице 1. В этой таблицы использованы следующие аббревиатуры:
Ac ацетил
Azt азетидинил
Bu бутил
cBu циклобутил
iBu изобутил
sBu втор-бутил
tBu трет-бутил
Bz бензил
Et этил
Fur фурил
Hx гексил
cHx циклогексил
Isox изоксазолил
Lac лактам, то есть 5-γ-Lac формулы

Me метил
Ph фенил
Pip пиперидил
Pn пентил
cPn циклопентил
Pr пропил
cPr циклопропил
iPr изопропил
Pym пиримидил
Pyr пиридил
Pyrd пирролидинил
Thdn тиазолидинил
Thi тиенил
Thiz тиазолил
Из перечисленных выше соединений предпочтительными являются соединения N 9, 16, 26, 28, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 46, 47, 48, 49, 51, 63, 64, 65, 66, 69, 74, 75, 76, 77, 78, 81, 89, 91, 95, 96, 107, 110, 112, 121, 132, 138, 139, 140, 144, 145, 148, 151, 160, 161, 164, 165, 171, 174, 181, 191, 193, 198, 199, 200, 201, 202, 205, 209, 211, 212, 213, 214, 218, 228, 229, 230, 231, 234, 240, 241, 242, 243, 246, 256, 272, 277, 286, 289, 297, 309, 310, 313, 316, 320, 325, 326, 329, 330, 332, 333, 335, 336, 337, 339, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 362, 363, 366, 367, 369, 372, 380, 381, 392, 399, 429, 431, 452, 453, 455, 457, 458, 461, 465, 466, 467, 468, 469, 470, 472, 473, 474, 475, 476, 484, 485, 488, 489, 490, 491, 494, 500, 501, 503, 504, 547, 548, 551, 552 и 553.Examples of certain compounds of the present invention are such compounds of formula (I):

in which the substituents have the meanings indicated in table 1. The following abbreviations are used in this table:
Ac acetyl
Azt azetidinyl
Bu butyl
cBu cyclobutyl
iBu has invented
sBu sec-butyl
tBu tert-butyl
Bz benzyl
Et ethyl
Fur furry
Hx hexyl
cHx cyclohexyl
Isox isoxazolyl
Lac lactam, i.e. 5-γ-Lac formulas

Me methyl
Ph phenyl
Piperidil pip
Pentyl pentyl
cPn cyclopentyl
Pr cut
cPr cyclopropyl
iPr isopropyl
Pym pyrimidyl
Pyr pyridyl
Pyrd pyrrolidinyl
Thdn thiazolidinyl
Thi thienyl
Thiz thiazolyl
Of the above compounds, preferred are compounds N 9, 16, 26, 28, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 46, 47, 48, 49, 51, 63, 64, 65, 66, 69, 74, 75, 76, 77, 78, 81, 89, 91, 95, 96, 107, 110, 112, 121, 132, 138, 139, 140, 144, 145, 148, 151, 160, 161, 164, 165, 171, 174, 181, 191, 193, 198, 199, 200, 201, 202, 205, 209, 211, 212, 213, 214, 218, 228, 229, 230, 231, 234, 240, 241, 242, 243, 246, 256, 272, 277, 286, 289, 297, 309, 310, 313, 316, 320, 325, 326, 329, 330, 332, 333, 335, 336, 337, 339, 346, 347, 348, 349, 350, 351, 352, 353, 354, 355, 362, 363, 366, 367, 369, 372, 380, 381, 392, 399, 429, 431, 452, 453, 455, 457, 458, 461, 465, 466, 467, 468, 469, 470, 472, 473, 474, 475, 476, 484, 485, 488, 489, 490, 491, 494, 500, 501, 503, 504, 547, 548, 551, 552 and 553.

 More preferred are compounds N 9, 26, 42, 46, 63, 64, 65, 91, 96, 121, 144, 165, 171, 191, 209, 213, 214, 313, 320, 336, 457, 547, 548 and 553.

Most preferred are compounds N:
46. 13- [2- (4-Cyanoacetylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ⁴ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4 -HCOCH ₂ CN, n = 0)];
91. 13- {2- [4- (N-Acetylglycyl) aminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ⁴ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOCH ₂ NHAc, n = 0)];
96. 13- {2- [4- (N-methoxycarbonylglycyl) methylaminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ₃ = 4-N (Me) COCH ₂ HCOOMe, n = 0)];
121. 13- [2- (4-Methoxycarbonylaminophenyl) -2-methylpropionyloxy] - 5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4 -NNCOOMe, n = 0)];
144. 13- {2- [4- (N-Phenylcarbamoylamino) phenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ R ³ = 4-NHCOHPh, n = 0)];
165. 13- {2- [4- (2-Oxoxoxolin-3-yl) phenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z = > C (Me) ₂ , R ³ = 4- (2-oxo-1,3-oxazolin-3-yl, n = 0)];
171. 13- [1- (4-Aminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NH ₂ , n = 0)];
191. 13- [1- (4-Acetylaminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHAc , n = 0)];
214. 13- [1- (4-Acetoxyacetylaminophenyl) cyclopentanecarbonyl-oxy] - 5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4 -NHCOCH ₂ OAc, n = 0)];
313. 13- [1- (4-Methanesulfonylaminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomethylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHSO ₂ Me, n = 0)];
336. 13- [1- (4-Acetylaminophenyl) -1-ethylbutyryloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Et) ₂ , R ³ = 4 -NHAc, n = 0)]; and
457. 13- [1- (4-Acetylaminophenyl) cyclobutanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₃ , R ³ = 4-NHAc , n = 0)].

 Compounds of the present invention can be obtained using known methods used to obtain compounds of this type, in particular, as described below.

 For example, the compounds of the present invention can be obtained in accordance with reaction schemes A and B (see the end of the description).

In the above formulas:
R ¹ , X, Z, n and Me are as defined above;
R ^3a represents any group indicated for the symbol R ³ , except for an amino group or a substituted amino group; the compound of formula (Ia) refers to compounds of formula (I), but has a group R ^3a in the phenyl ring instead of the group R ³ ; the compound of formula (Ia ¹ ) refers to compounds of formula (I), but has a nitro group in the phenyl ring instead of the group R ³ ; the compound of formula (Ib) refers to compounds of formula (I), but has an amino group in the phenyl ring instead of the group R ³ ;
R ^3c represents a substituted amino group, which is included in the definition of R ³ ; the compound of formula (Ic) refers to compounds of formula (I), but has a group R ^3c in the phenyl ring instead of the group R ³ .

 Derivatives of 15-hydroxymethylbemycin of formula (III), which are used as starting materials in the implementation of this method, are known compounds that are discussed, for example, in Japanese patent application Sho 60-18191.

в присутствии сильной органической кислоты, такой как трифторметансульфоновая кислота.Stage A1
At this stage, a compound of formula (IV) is obtained by reacting a compound of formula (III) with a carboxylic acid or alcohol of formula (V):

in the presence of a strong organic acid such as trifluoromethanesulfonic acid.

 A strong organic acid, for example trifluoromethanesulfonic acid, acts as a catalyst, therefore, in principle, only a catalytic amount of this acid should be used. However, the amount required can vary widely depending on the reactivity of the carboxylic acid or alcohol of formula (V) used. Typically, the required amount of trifluoromethanesulfonic acid should not exceed an equimolar amount with respect to the compound of formula (V).

 The addition of a powdered inorganic compound to the reaction mixture in some cases can accelerate the reaction. Examples of suitable inorganic compounds having such properties are metal salts, in particular copper trifluoromethanesulfonate, copper iodide, tin iodide, cobalt iodide or nickel iodide, a Celite filter (trademark), silica gel or alumina. Of these materials, copper salts, in particular copper trifluoromethanesulfonate or copper iodide, are preferred, and copper iodide is most preferred.

 This reaction is usually and preferably carried out in the presence of a solvent. Any solvent can be used provided that it does not adversely affect the course of the reaction or the starting materials used and is capable of at least slightly dissolving the reagents. Examples of suitable solvents are aromatic hydrocarbons such as benzene, toluene or xylene; halogenated hydrocarbons such as methylene chloride, 1,2-dichloroethane or chloroform; esters such as ethyl acetate or propyl acetate; ethers such as diethyl ether, tetrahydrofuran, dioxane or dimethoxyethane; amides such as dimethylformamide, dimethylacetamide or hexamethylphosphoric triamide; sulfoxides such as dimethyl sulfoxide; and nitriles such as acetonitrile.

The interaction can be carried out in a wide temperature range, and the exact reaction temperature is not critical to achieve the objectives of the present invention. The preferred reaction temperature depends on factors such as the nature of the solvent and the starting materials or reagents used. However, this reaction is best carried out at a temperature of from -10 ^o C to 100 ^o C, preferably at a temperature of from 0 ^o C to 50 ^o C. The time required for interaction can also vary within wide limits depending on many factors, in particular on the reaction temperature, the nature of the reagents and solvent used. However, if the reaction is carried out under the above preferred conditions, it usually lasts from 5 minutes to 6 hours, preferably from 10 minutes to 2 hours.

Stage A2
In this step, a compound of formula (Ia) is prepared by reacting a compound of formula (IV) with hydroxylamine or a salt thereof to convert the carbonyl group at position 5 to a hydroxyimino group.

 Various types of hydroxylamine salts can be used to carry out this reaction. Examples of acceptable salts are salts formed with inorganic acids, such as hydrochloride or sulfate, and salts formed with organic acids, such as acetate or oxalate. Of these, the most preferred salt is hydrochloride.

 This reaction is usually and preferably carried out in the presence of a solvent. Any solvent can be used provided that it does not adversely affect the course of the reaction or the starting materials used and is capable of at least slightly dissolving the reagents. Examples of suitable solvents are lower alcohols that are readily miscible with water, such as methanol, ethanol or propanol, or a mixture of an ether, such as tetrahydrofuran or dioxane, with water.

The interaction can be carried out in a wide temperature range, and the exact reaction temperature is not critical to achieve the objectives of the present invention. The preferred reaction temperature depends on factors such as the nature of the solvent and the starting materials or reagents used. However, this reaction is best performed at temperatures from 0 ^° C. to 50 ^° C. The time required for the reaction can also vary widely depending on many factors, in particular the reaction temperature, the nature of the reagents used and the solvent. However, if the reaction is carried out under the preferred conditions outlined above, it usually lasts from 1 to 10 hours.

Stage B1
Prior to step B1, the hydroxyimino group in compound (Ia ¹ ) can be protected with an acid-resistant protecting group, such as a tert-butyldimethylsilyl group. The protective group can be introduced by known methods, for example, those described in the work of W. Green and P. G. M. Wat "Protective Group in Orgaic Synthesis", 2nd edition, publisher "John Wiley and Sons Inc.", New York (1991), which is included in this description of the invention as opposed material.

In step B1, a compound of formula (Ib) containing an amino group is prepared by reducing a nitro group in a compound of formula (Ia ¹ ), i.e., a compound of formula (Ia) in which R ^3a represents a nitro group.

 The restoration of the nitro group can be carried out by known methods. An example of an acceptable reduction process is catalytic reduction using a noble metal catalyst, for example, palladium carbon, palladium barium sulfate or platinum oxide.

 This reaction is usually and preferably carried out in the presence of a solvent. Any solvent can be used provided that it does not adversely affect the course of the reaction or the starting materials used and is capable of at least slightly dissolving the reagents. Examples of suitable solvents are alcohols, such as methanol or ethanol, ethers, such as tetrahydrofuran or dioxane, and esters, such as ethyl acetate.

The interaction can be carried out in a wide temperature range, and the exact reaction temperature is not critical to achieve the objectives of the present invention. The preferred reaction temperature depends on factors such as the nature of the solvent and the starting materials or reagents used. However, this reaction is best carried out at a temperature of from 10 ^° C. to 80 ^° C. The time required for the reaction can also vary widely depending on many factors, in particular the reaction temperature, the nature of the reagents used and the solvent. However, if the reaction is carried out under the preferred conditions outlined above, it usually lasts from 10 minutes to 5 hours.

 Another preferred reduction method is reduction with zinc powder in a solvent such as acetic acid.

The interaction can be carried out in a wide temperature range, and the exact reaction temperature is not critical to achieve the objectives of the present invention. The preferred reaction temperature depends on factors such as the nature of the solvent and the starting materials or reagents used. However, this reaction is best carried out at a temperature of from 0 ^o C to room temperature. The time required for the interaction can also vary widely depending on many factors, in particular on the reaction temperature and the nature of the reagents and solvent used. However, if the reaction is carried out under the above preferred conditions, then it usually lasts from 30 minutes to 12 hours.

 A more preferred reduction method is reduction with sodium borohydride in the presence of a nickel catalyst. Suitable nickel catalysts are nickel salts such as nickel chloride or bromide and triphenylphosphine complexes of these nickel salts. Triphenylphosphine complexes are preferred.

 This reaction is usually and preferably carried out in the presence of a solvent. Any solvent can be used provided that it does not adversely affect the course of the reaction or the starting materials used and is capable of at least slightly dissolving the reagents. Examples of suitable solvents are alcohols, such as methanol or ethanol, and ethers, such as tetrahydrofuran or dioxane.

The interaction can be carried out in a wide temperature range, and the exact reaction temperature is not critical to achieve the objectives of the present invention. The preferred reaction temperature depends on factors such as the nature of the solvent and the starting materials or reagents used. However, this reaction is best carried out at a temperature of from 0 ^o C to room temperature. The time required for the interaction can also vary widely depending on many factors, in particular on the reaction temperature and the nature of the reagents and solvent used. However, if the reaction is carried out under the preferred conditions outlined above, it usually lasts from 10 to 120 minutes.

Stage B2
At this stage, a compound of formula (Ic) containing a substituted amino group (A-NH) is prepared by reacting an amino group in a compound of formula (Ib) with an acid or reactive derivative having the formula A-OH (A has the meanings indicated below) or with an isocyanate or isothiocyanate, presented below.

A represents one of the following groups of the formula:
R ⁴ -CO - (x)
R ⁶ R ⁷ NC (= Y) - - (xi) R ⁶ ≠ H
R ⁸ SO ₂ - - (xii)
R ⁹ OC (= O) - - (xiii)
R ¹⁰ c (= NOR ¹¹ ) C (= O) - - (xiv)
The isocyanates and isothiocyanates mentioned above have the following formula:
R ⁷ N = C = Y - (xv)
In the above formulas, the elements R ⁴ , R ⁶ , R ⁷ , R ⁸ , R ⁹ , R ¹⁰ , R ¹¹ and Y have the above meanings.

 There are no restrictions on the nature of the derivatives that interact with the acid, so any such derivatives commonly used in this type of condensation reaction can be used. Examples of acid-reactive derivatives are acid halides such as acid chloride or bromohydride, acid anhydride, mixed acid anhydride, active ester or active amide.

 If an acid of formula A-OH is used, a desiccant such as dicyclohexylcarbodiimide, 2-chloro-1-methylpyridinium iodide, p-toluenesulfonic acid or sulfuric acid should be used, the preferred desiccant is 2-chloro-1-methyl-pyridinium iodide. The amount of desiccant is usually 1 to 5 moles, preferably 1 to 2 moles, per mole of acid used (A-OH).

 This reaction is usually and preferably carried out in the presence of a solvent. Any solvent can be used provided that it does not adversely affect the course of the reaction or the starting materials used and is capable of at least slightly dissolving the reagents. Examples of suitable solvents are hydrocarbons such as hexane, petroleum ether, benzene or toluene, halogenated hydrocarbons such as chloroform, methylene chloride or 1,2-dichloroethane; amides such as dimethylformamide; sulfoxides such as dimethyl sulfoxide; nitriles such as acetonitrile; or a mixture of any two or more solvents, with methylene chloride or 1,2-dichloroethane being the most preferred solvent.

The interaction can be carried out in a wide temperature range, and the exact reaction temperature is not critical to achieve the objectives of the present invention. The preferred reaction temperature depends on factors such as the nature of the solvent and the starting materials or reagents used. However, this reaction is best carried out at a temperature of from -70 ^o C to 90 ^o C, preferably from 0 ^o C to 60 ^o C. The time required for interaction can also vary widely depending on many factors, in particular temperature the reaction and nature of the reagents and solvent used. However, if the reaction is carried out under the preferred conditions outlined above, it usually lasts from 15 minutes to 24 hours, preferably from 30 minutes to 6 hours.

 When using an acid halide of the formula A-OH, this reaction is preferably carried out in the presence of a base. There is no restriction on the nature of the base, so any base commonly used in reactions of this type can be used. Examples of such bases are organic bases such as triethylamine, dimethylaniline, pyridine, 4-dimethylaminopyridine, 1,5-diazabicyclo [4.3.0] nonen-5 (DBN) and 1,8-diazabicyclo [5.4.0] undecene-7 ( DBU).

 The amount of acid halide of the formula A-OH is preferably from 1 to 10 moles, and the base is from 2 to 8 moles per mole of the compound of formula (Ib).

 Preferred solvents are the same solvents that are used with the corresponding carboxylic acid.

The interaction can be carried out in a wide temperature range, and the exact reaction temperature is not critical to achieve the objectives of the present invention. The preferred reaction temperature depends on factors such as the nature of the solvent and the starting materials or reagents used. However, this reaction is best carried out at a temperature of from 0 ^° C. to 50 ^° C. The time required for the reaction can also vary widely depending on many factors, in particular the reaction temperature and the nature of the reagents and solvent used. However, if the reaction is carried out under the preferred conditions outlined above, it usually lasts from 5 minutes to 2 hours.

 When using isocyanate or isothiocyanate, this reaction is carried out in the presence of a solvent. Preferred solvents are the same solvents that have been recommended above for use with carboxylic acid. Reaction conditions, in particular temperature and time, also correspond to the same parameters recommended above when using carboxylic acid.

Compounds in which R ³ represents a group of formula (v) or (vi) can be prepared without using a compound of formula A-OH, isocyanate or isothiocyanate.

 If the hydroxyimino group is protected by a silyl group, then this protective group is removed by treatment with an acid in a solvent in the last reaction step.

 There are no restrictions on acidic catalysts for this invention, so any acidic catalysts used in reactions of this type can be used. Examples of such acid catalysts are hydrochloric acid, hydrobromic acid, hydroiodic acid, sulfuric acid, methanesulfonic acid or toluenesulfonic acid.

The reaction can take place over a wide range of temperatures, with the precise reaction temperature not critical to achieving the objectives of the present invention. The preferred reaction temperature depends on factors such as the nature of the solvent and the starting materials or reagents used. However, this reaction is best carried out at a temperature of from -100 ^o C to 100 ^o C, preferably from 0 ^o C to 50 ^o C. The time required for interaction can also vary within wide limits depending on many factors, in particular temperature the reaction and nature of the reagents and solvent used. However, if the reaction is carried out under the above preferred conditions, it usually lasts from 5 minutes to 6 hours, preferably from 10 minutes to 2 hours.

 This reaction is usually and preferably carried out in the presence of a solvent. Any solvent may be used provided that it does not adversely affect the course of the reaction or the starting materials used and is capable of at least slightly dissolving the reactants. Examples of suitable solvents are lower alcohols that are readily miscible with water, in particular methanol, ethanol or propanol, a mixture of an ether such as tetrahydrofuran or dioxane with water.

 Milbemycins and their natural analogues, which can be used as starting materials for the synthesis of compounds of formula (III), are usually obtained in the form of mixtures with different ratios of these compounds, and they can interact after separation into fractions or in the form of mixtures, regardless of whether whether they are natural or artificially obtained mixtures. Therefore, the compound used at each station of the above reactions may be either a single compound or a mixture of compounds. Thus, the compound of formula (I) can be obtained as a separate compound or as a mixture of compounds. If it is obtained as a mixture of compounds, then it can be used as is or divided into separate compounds before use.

After performing each step of the compound of formula (IV), (Ia), (Ia ¹ ), (Ib) or (Ic), it can be isolated from the reaction mixture using known methods and, if necessary, purified, for example, by column chromatography.

В этих формулах X и Z имеют указанные выше значения, а m' означает 0 или целое число от 1 до 3.The compound of formula (V), which is another starting material for the implementation of this method, exists in the form of various compounds that differ in the nature of the groups Z and X attached via an optional oxygen atom to the phenyl ring, and can be expressed by the following formulas (Va) , (Vb), (Vc) and (Vd):

In these formulas, X and Z have the above meanings, and m 'is 0 or an integer from 1 to 3.

 These compounds can be obtained using a combination of known synthesis methods using commercially available reagents, as described in paragraphs (1) and (2) below.

(1) If n = 1:
α-Alkyl-α-haloalkanoate, which can be purchased or obtained by α-alkylation of a commercially available alkanoate with a base and an alkyl halide followed by α-halogenation, is reacted with phenol in the presence of a base, resulting in the formation of α- (phenoxy) α-alkylalkanoate. By hydrolysis of this ester, a carboxylic acid of the formula (Va) is obtained. If a dihaloalkane such as 1,2-dibromoethane, 1,3-dibromopropane or 1,4-dibromopentane is used as the alkyl halide, a cycloalkane carboxylic acid of the formula (Vc) can be obtained. The carboxylic acid thus obtained is reduced with a metal hydride such as lithium aluminum hydride to form an alcohol of the formula (Vb) or (Vd).

(2) If n = 0:
The α-phenyl-α, α-α-dialkyl acetate, which is obtained by α-α-alkylation of commercially available phenylacetate with a base and an alkyl halide, is hydrolyzed to form a carboxylic acid of the formula (VIIa). If a dihaloalkane such as 1,2-dibromoethane, 1,3-dibromopropane or 1,4-dibromopentane is used as the alkyl halide, a cycloalkane carboxylic acid of the formula (Vc) can be obtained. The carboxylic acid thus obtained is reduced with a metal hydride such as lithium aluminum hydride to form an alcohol of the formula (Vb) or (Vd).

 The compounds of the present invention have a strong acaricidal effect. In addition, they successfully act on ticks that are difficult to kill with known acaricides and do a lot of harm.

 The compounds of the present invention also have a strong insecticidal effect on fleas, which are quite immune to other milbemycin compounds, and therefore can be used as insecticides. The active compounds of the present invention are able to have a prophylactic effect on harmful insects, while they do not exhibit phytotoxicity, so agricultural plants are not damaged. The compounds of the present invention can be used to kill a variety of harmful insects, including those that infect plants by sucking juice or eating them, parasitize on plants, infect materials stored in warehouses, are unacceptable by sanitary standards, and other insects. These compounds also effectively kill various nematodes that infect pets.

 If the compounds of the present invention are used as anthelmintic agents for treating animals, including humans, they can be administered orally as a liquid drink. This drink is a solution, suspension or dispersion of the active compound in an aprotic non-toxic solvent or water in admixture with a suspending agent such as bentonite, a wetting agent or other excipients. This drink may also contain antifoam. The active compound is usually present in this drink in an amount of from 0.01 to 0.5 weight percent, preferably from 0.01 to 0.1 weight percent.

 Alternatively, these compositions can be administered orally in the form of dry solids, preferably in a dosage form, such as capsules, pills or tablets containing the necessary amount of active compound. These compositions can be obtained by uniformly mixing the active compound with suitable sprayed diluents, fillers, dispersants and / or binders, for example, starch, lactose, talc, magnesium stearate and gum. The mass and content of the components in this composition can vary widely depending on the type of animal to which treatment is prescribed, the degree of damage, the type of insect parasite and the body weight of the animal.

 These compounds can also be included as additives in animal feed, in which case they can be uniformly dispersed in the feed, scattered over its surface, or used in the form of granules. The content of active compound in the feed is preferably from 0.0001 to 0.02% to achieve the desired anthelmintic effect.

 The compounds of the present invention, dissolved or dispersed in a liquid vehicle, can be administered parenterally to the animals by injection into the pancreas, muscle or trachea, or by subcutaneous injection. In the case of parenteral administration, the active compound is preferably mixed with a suitable vegetable oil, such as peanut or cottonseed. The active compound content in the preparation is usually from 0.05 to 50 weight percent.

 The compounds of the present invention are suitable for topical use with an acceptable excipient such as dimethyl sulfoxide or a hydrocarbon solvent. Such preparations are applied directly to the animal by spraying or immersion in a solution.

 The dose of the active compound can vary widely depending on the type of animal, as well as the nature and extent of infection with insect parasites. However, better results are achieved when administered orally, when the dose is from 0.01 to 100 mg, preferably from 0.5 to 50 mg, per 1 kg of animal body weight. This compound can be administered in one or more doses over a short period of time, in particular from 1 to 5 days.

 If the composition of the present invention is intended for use in agriculture or horticulture, it can be used in various forms and preparations. For example, it can be obtained in the form of dusts, coarse powders, soluble powders, micro granules, finely divided micro granules, wettable powders, diluted emulsions, emulsifiable concentrates, aqueous or oily suspensions, aqueous or oily solutions (which can be used for direct atomization or dilution), aerosol or capsules in polymeric substances. The excipient used may be natural or synthetic, organic or inorganic, and is usually used to improve exposure, facilitate storage, transportation, or handling of the active compound. Solid, liquid and gaseous fillers for a composition of this type may be selected from fillers known in the art.

 Such compositions can be obtained by known methods, for example by uniformly mixing and / or grinding the active ingredients with a filler or diluent (solvent) or, optionally, with a surfactant, after which this mixture, if necessary, can be sprayed, granulated, tabletted, subjected absorption cleaning, in addition, a protective coating may be applied to it.

 Examples of fillers that can be used in the production of dusts, coarse powders, soluble powders, microgranules, finely divided microgranules, wettable and dispersible powders are clay of the kaolinite or pyrophyllite group, talc, calcium carbonate, clay of the montmorillonite group, in particular japanese bentonite or powder or granules of a natural mineral such as attapulgite, sepiolite, diatomaceous earth, pumice or silica sand, finely ground powder of an inorganic compound, that such as aqueous or anhydrous synthetic amorphous silicon dioxide or magnesium carbonate, sugar, in particular sucrose, lactose or glucose, organic matter such as starch, dextrin, fine crystalline cellulose, wood powder, ground coffee beans and ground straw, wheat flour or ground buckwheat a suspension or salt of an inorganic compound, for example, sodium sulfate, sodium carbonate, sodium bicarbonate, sodium phosphate, calcium sulfate or ammonium sulfate and urea.

 Examples of suitable solvents are high boiling point aromatic solvents such as xylene, methylnaphthalene, alkylbenzenes or phenylxylene ethane, high boiling point paraffinic or naphthenic solvents, ethers of various carboxylic acids, in particular oleic acid, adipic acid, lauric acid, fatty acid coconut oil, maleic acid and phthalic acid, various phosphates, ketones, in particular cyclohexanone or methyl isobutyl ketone, polar solvents, such as to N-alkylpyrrolidones or dimethyl sulfoxide, glycols such as ethylene glycol, propylene glycol, butanediol or hexylene glycol, their polymers, ethers or esters, alcohols, in particular methanol, ethanol, propanol, butanol, hexanol, octanol or lauryl alcohol, or esters, optionally epoxidized vegetable oils, such as coconut or soybean oil, or water.

 Surfactants can be cationic, anionic or non-ionic compounds having good emulsifying, dispersing or wetting properties, in particular those that are commonly used in compositions of this type. You can also use one surfactant or a mixture of two or more such substances.

 Suitable non-ionic surfactants include polyoxyethylene alkyl ethers, polyoxyethylene alkyl esters, polyoxyethylene alkyl aryl ethers, polyoxyethylene aryl ethers, polyoxyethylene sorbitalkyl esters, sugar sorbitol esters, sugar fatty acid esters, glycerol esters, and fatty acid glycerol esters "pluronic", acetylene alcohol or acetylenediol or ethylene oxide in the form of additives, surface-active silicic substance groups and alkyl glucosides.

-олефинсульфоновых кислот.Suitable anionic surfactants include salts of alkylbenzenesulfonic acid, salts of dialkyl sulfosuccinic acid, salts of alkyl sulfates, salts of alkyl methyl tauride, anionic surfactants which are prepared by esterification of the aforementioned non-ionic surfactant with ethylene dioxide with sulfuric or phosphoric acid, if necessary, with subsequent neutralization with an acceptable alkali; salts of ligninsulfonic acid, salts of (alkyl) naphthalenesulfonic acid or their condensates, salts of phenolsulfonic acid or their condensates, polyelectrolytes of polycarboxylic acid or polysulfonic acid, consisting of a salt of a condensate, for example, acrylic acid, maleic acid, stylinsulfonic acid or a vinyl radical; starch-type surfactants, including a mixture of starch or dextrin with 1- (2-octenoyl) sodium succinate, carboxymethyl cellulose salts, a soap such as a sodium or potassium salt of a higher fatty acid, and salts

olefin sulfonic acids.

 Suitable cationic surfactants include amine or quaternary ammonium salt surfactants and ethylene dioxide obtained by the addition of a higher aliphatic amine or fatty acid amide.

 Suitable amphoteric surfactants include amino acid or betaine type surfactants or lecithin.

 All of the above surfactants and their derivatives, in the molecule of which one or all of the hydrogen atoms are replaced by fluorine atoms, have the ability to reduce strong surface tension and can be used with a high degree of efficiency.

 The compositions of the present invention may also contain one or more additives selected from the group of stabilizers, anti-foaming agents, viscosity regulators, binders and adhesives, or combinations thereof, as well as fertilizers and other active substances to achieve a special effect.

 Insecticidal and acaricidal compositions usually contain from 0.01 to 99%, preferably from 0.1 to 95%, of the active compound, from 1 to 99.99% of a solid or liquid filler, and from 0 to 25%, preferably from 0.1 to 25% surfactant. Products manufactured by industry are usually sold in the form of concentrated formulations, which are diluted before use to a concentration of 0.001 to 0.0001 weight percent (10 to 1 part per million).

 All percentages are by weight.

 The compounds of the present invention can be mixed or used together with other active compounds, for example, insecticides, poisonous food, bactericides, acaricides, non-germicides, fungicides, plant growth regulators or herbicides. Examples of these insecticides include organic phosphoric chemicals, carbamate chemicals, carboxylate chemicals, chlorinated hydrocarbon chemicals and insecticidal substances formed by microorganisms.

 The compounds of the present invention can also be mixed or used together with synergists. Preparations with such chemicals and their intended use must be commercially useful. A synergist, regardless of its action, is itself a compound capable of enhancing the action of active substances.

Biological activity
The following biological test examples provide an even better understanding of the effects of the compounds of the present invention.

Сравнительное соединение 2:

Сравнительное соединение 3:

Пример испытания
Испытание инсектицидного действия против кошачьих блох.In Table 2 below, Comparative Compound 1 is 5-hydroxyiminomylbemycin A ₄ (milbemycin A ₄ oxime) described in Japanese Patent Application Examples Sho 60-142991; Comparative Compound 2 is one of the compounds discussed in the examples of Japanese Patent Application Hei 5-255343; and comparative compound 3 is one of the compounds shown in the examples of Japanese patent application Sho 63-10791, the structural formulas of which are given below [in these formulas Me means methyl]:
Comparative Compound 1:

Comparative Compound 2:

Comparative Compound 3:

Test example
Test the insecticidal effect against cat fleas.

A container was made in which the flea’s living space was isolated from bovine serum using parafilm (which is commonly used as artificial skin). The test compound was added to bovine serum in an amount sufficient to achieve a concentration of 1 part per million, after which the fleas could suck the serum through parafilm at a temperature of 37 ^o C. Each group included 20 fleas. After 48 hours, the number of dead fleas was counted and the insecticidal effect of this drug was evaluated. The mortality rate was adjusted by counting dead fleas in the control group that did not receive the drug of the present invention. The results are shown in table 2.

Example 1
13- [2- (4-Nitrophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NO ₂ , n = 0 (compound N 2)]
1 (a) 13- [2- (4-Nitrophenyl) -2-methylpropionyl] -5-oxomylbemycin A ₄ [(IV); R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NO ₂ , n = 0
212 mg (1.01 mmol) of 2- (4-nitrophenyl) -2-methylpropionic acid and 15 ml of trifluoromethanesulfonic acid were added under argon gas flow under ice cooling to a solution of 188 mg (0.34 mmol) of 15-hydroxy-5-oxomylbemycin A ₄ in 8 ml of methylene chloride, after which this mixture was stirred for 30 minutes at room temperature. After this time, the reaction solution was poured into water and extracted with ethyl acetate. The extract was washed with 5% (w / v) aqueous sodium bicarbonate and saturated aqueous sodium chloride, after which the solution was dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The residue was purified by silica gel column chromatography using an ethyl acetate / hexane mixture with a volume ratio of 4: 6 as eluent, whereby 502 mg (58% yield) of the title compound was obtained.

 Nuclear Magnetic Resonance Spectrum (270 MHz) δ ppm: 8.16 (2H, doublet, J = 9.8 Hz), 6.54 (1H, triplet, J = 1.8 Hz), 5.92-5 69 (2H, multiplet), 5.47-5.29 (3H, multiplet), 4.91 (1H, doublet, J = 10.5 Hz), 4.70 (2H, broad singlet), 3.84 (1H, singlet); 1.63 (6H, singlet).

1 (b) 13- [2- (4-Nitrophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄
186 mg (0.25 mmol) of 13- [2- (4-nitrophenyl) -2-methylpropionyl] -5-oxomylbemycin A ₄ [prepared as described above in paragraph (a)] was dissolved in 1.5 ml of dioxane. To the resulting solution was added 0.75 ml of water, 1.5 ml of methanol and 165 mg of hydrochloric hydroxylamine, after which this mixture was stirred for 3 hours at a temperature of 40 ^o C. After this time, the reaction solution was diluted with 20 ml of ethyl acetate and washed three times with water . The solution was then dried over anhydrous magnesium sulfate, and the solvent was removed by distillation under reduced pressure. The resulting residue was purified by silica gel column chromatography using a mixture of ethyl acetate and hexane with a volume ratio of 5: 5 as eluent, whereby 170 mg (89.2% yield) of the title compound was obtained.

 Nuclear Magnetic Resonance Spectrum (270 MHz) δ ppm: 8.17 (2H, doublet, J = 8.7 Hz), 8.00 (1H, broad singlet), 7.47 (2H, doublet, J = 8 , 7 Hz), 5.90-5.71 (3H, multiplet), 5.48-5.27 (3H, multiplet), 4.91 (1H, doublet, J = 10.6 Hz), 4.70 and 4.68 (2H, AB-quartet, J = 15.0 Hz), 4.65 (1H, singlet), 3.97 (1H, singlet), 3.57 (1H, multiplet), 3.36 ( 1H, multiplet), 3.04 (1H, doublet of triplets, J = 2.3 and 9.3 Hz), 1.93 (3H, singlet), 1.63 (3H, singlet), 1.60 (3H, singlet), 1.29 (3H, singlet), 0.99 (3H, triplet, J = 7.3 Hz), 0.82 (6H, doublet, J = 6.5 Hz).

Examples 2-8
In accordance with the procedure described in example 1, the compounds of examples 2-8 were obtained. The output values are calculated as the total value for points (a) and (b).

Example 2
13- [2- (3-Nitrophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 3-NO ₂ , n = 0 (compound N 3)]
Yield: 64.3%
Nuclear Magnetic Resonance Spectrum (270 MHz) δ ppm: 8.19 (1H, doublet of doublets, J = 1.9 and 1.9 Hz), 8.12 (1H, doublet of doublets, J = 1.9 and 7 , 9 Hz), 7.63 (1H, doublet of doublets, J = 1.9 and 7.9 Hz), 7.49 (1H, doublet of doublets, J = 7.9 and 7.9 Hz), 5.90 -5.70 (3H, multiplet), 5.47-5.29 (3H, multiplet), 4.92 (1H, doublet, J = 10.6 Hz), 4.73 and 4.68 (2H, AB quartet, J = 14.4 Hz), 4.66 (1H, singlet), 3.97 (1H, singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, doublet of triplets, J = 2.1 & 9.1 Hz), 1.93 (3H, singlet), 1.66 (3H, singlet), 1.61 (3H, singlet), 1.29 (3H singlet), 0.96 (3H, triplet, J = 7.3 Hz), 0.84 (3H, doublet, J = 6.5 Hz), 0.83 (3H, doublet, J = 6.4 Hz )

Example 3
13- [2- (4-Methoxyphenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-MeO , n = 0 (compound N 16)] Mass spectrum (FAB-MS) m / z: 748 (M + H ⁺ , M = C ₄₃ H ₅₇ NO ₁₀ ).

 (FAB-MS means the mass spectrum obtained by bombardment by accelerated atoms).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.95 (1H, broad singlet), 7.22 (2H, doublet, J = 8.8 Hz), 6.83 (2H, doublet, J = 8 8 Hz), 4.86 (1H, doublet, J = 10.5 Hz), 4.73 and 4.68 (2H, doublet of AB quartets, J = 1.8 and 14.4 Hz), 4, 65 (1H, singlet), 3.96 (1H, singlet), 3.79 (3H, singlet), 3.56 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, doublet doublets, J = 2.2 and 9.2 Hz), 1.93 (3H, singlet), 1.56 (3H, singlet), 1.53 (3H, singlet), 1.30 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (3H, doublet, J = 6.4 Hz), 0.82 (3H, doublet, J = 6.4 Hz).

Example 4
13- [1- (4-Methoxyphenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I); R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-MeO, n = 0 (compound N 181)]
Mass spectrum (FAB-MS) m / z: 774 (M + H ⁺ , M = C ₄₅ H ₅₉ NO ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.25 (2H, doublet, J = 8.6 Hz), 6.81 (2H, doublet, J = 8.6 Hz), 4.80 (1H doublet, J = 10.6 Hz), 4.72 and 4.70 (2H, AB quartet, J = 14.4 Hz), 4.65 (1H, singlet), 3.96 (1H, singlet) , 3.78 (3H, singlet), 3.56 (1H, multiplet), 3.36 (1H, multiplet), 3.02 (1H, doublet of doublets, J = 2.2 and 9.2 Hz), 2 66-2.54 (2H, multiplet), 1.93 (3H, singlet), 1.29 (3H, singlet), 0.97 (3H, triplet, J = 7.3 Hz), 0.82 ( 3H, doublet, J = 6.6 Hz); 0.77 (3H, doublet, J = 5.9 Hz).

Example 5 13- [2- (4-Isobutoxyphenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) _{) 2} , R ³ = 4-OiBu, n = 0 (compound N 23)]
Mass spectrum (FAB-MS) m / z: 790 (M + H ⁺ , M = C ₄₆ H ₆₀ NO ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.85 (1H, broad singlet), 7.20 (2H, doublet, J = 8.6 Hz), 6.81 (2H, doublet, J = 8 , 6 Hz), 4.86 (1H, doublet, J = 10.0 Hz), 4.75 and 4.66 (2H, AB quartet, J = 14.4 Hz), 4.65 (1H, singlet ), 3.96 (1H, singlet), 3.71 (2H, singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 1.93 (3H, singlet), 1.55 (3H, singlet), 1.53 (3H, singlet), 1.31 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0 88-0.80 (6H, multiplet).

Example 6
13- [1- (4-Nitrophenyl) cyclopropanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₂ , R ³ = 4-NO ₂ , n = 0 (compound N 387)]
Nuclear Magnetic Resonance Spectrum (270 MHz) δ ppm: 8.18 (2H, doublet, J = 8.7 Hz), 7.51 (2H, doublet, J = 8.7 Hz), 5.82 (1H singlet), 5.90-5.71 (3H, multiplet), 5.46-5.27 (3H, multiplet), 4.91 (1H, doublet, J = 10.6 Hz), 4.72 and 4.66 (2H, AB quartet, J = 14.4 Hz), 4.65 (1H, singlet), 3.93 (1H, singlet), 3.55 (1H, multiplet), 3.35 (1H multiplet), 3.03 (1H, doublet of triplets, J = 2.2 & 9.2 Hz), 1.93 (3H, singlet), 1.36 (3H, singlet), 0.97 (3H, triplet , J = 7.3 Hz), 0.91 (3H, doublet, J = 6.5 Hz), 0.82 (3H, doublet, J = 6.5 Hz).

Example 7
13 [1- (4-Nitrophenyl) cyclobutanecarbonyloxy] -5-hydroxyiminomylbemycin R ⁴ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₃ , R ³ = 4-NO ₂ , n = 0 (compound N 451)]
Yield: 66.1%
Nuclear Magnetic Resonance Spectrum (270 MHz) δ ppm: 8.18 (2H, doublet, J = 8.9 Hz), 7.42 (2H, doublet, J = 8.9 Hz), 5.89-5 72 (3H, multiplet), 5.46-5.27 (3H, multiplet), 4.88 (1H, doublet, J = 10.5 Hz), 4.73 and 4.67 (2H, AB quartet) , J = 14 Hz), 4.66 (1H, singlet), 3.95 (1H, singlet), 3.56 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, doublet of triplets, J = 2.3 and 9.2 Hz), 1.93 (3H, singlet), 1.93 (3H, singlet), 1.35 (3H, singlet), 0.98 (3H, triplet, J = 73 Hz), 0.82 (3H, doublet, J = 6.4 Hz), 0.78 (3H, doublet, J = 6.6 Hz).

Example 8
13- [2- (4-Nitrophenyl) -2-methylpropyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CH ₂ , Z => C (Me) ₂ , R ³ = 4- NO ₂ , n = 0 (compound N 513)]
Yield: 65.3% g.

 Nuclear Magnetic Resonance Spectrum (270 MHz) δ ppm: 8.14 (2H, doublet, J = 8.9 Hz), 7.51 (2H, doublet, J = 8.9 Hz), 5.90-5 , 71 (3H, multiplet), 5.46 - 5.27 (3H, multiplet), 4.65 (1H, singlet), 3.94 (1H, singlet), 3.31 (1H, doublet, J = 9 , 0 Hz), 3.13 (2H, doublet, J = 9.0 Hz), 1.87 (6H, singlet).

Example 9
13- [2- (4-Aminophenyl) -2-methylpropionyloxy] -5-hydroxyimimomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NH ₂ , n = 0 (compound N 6)]
1.0 g (1.31 mmol) of 13- [2- (4-nitrophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ (prepared as described in Example 1) was dissolved in a mixture of 13 ml of methanol and 7 ml of tetrahydrofuran. To this solution, 85 mg (0.13 mmol) of a complex of triphenylphosphine with nickel (II) chloride and 100 mg (2.6 mmol) of sodium borohydride were added under ice cooling. The reaction mixture was stirred for 30 minutes, after which it was diluted with ethyl acetate, washed three times with water and dried over anhydrous sodium sulfate. The solution was removed by distillation under reduced pressure. The resulting residue was purified by silica gel column chromatography using ethyl acetate and hexane with a volume ratio of 5: 5 as eluent, whereby 802 mg (yield 83.8%) of the title compound was obtained.

 Nuclear Magnetic Resonance Spectrum (270 MHz) δ / ppm: 8.00 (1H, broad singlet), 709 (2H, doublet, J = 8.5 Hz), 6.62 (2H, doublet, J = 8, 5 Hz), 5.95-5.71 (3H, multiplet), 5.50-5.25 (3H, multiplet), 4.86 (1H, doublet, J = 10.5 Hz), 4.75 and 4.68 (2H, AB quartet, J = 15.0 Hz), 4.66 (1H, singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H triplet doublet, J = 2.1 and 9.0 Hz); 1.93 (3H, singlet), 1.54 (3H, singlet), 1.51 (3H, singlet), 1.32 (3H, singlet), 0.98 (3H, triplet, J = 7.2 Hz ), 0.82 (6H, doublet, J = 6.4 Hz).

Examples 10-13
In accordance with the procedure described in example 9, the compounds of examples 10-13 were obtained.

Example 10
13- [2- (3-Aminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 3-NH ₂ n = 0 (compound N 7)]
Nuclear Magnetic Resonance Spectrum (270 MHz) δ ppm: 7.42 (1H, multiplet), 7.21 (1H, multiplet), 6.90 (1H, multiplet), 5.90-5.70 (3H, multiplet), 5.48-5.29 (3H, multiplet), 4.89 (1H, doublet, J = 10.6 Hz), 4.73 and 4.68 (2H, AB quartet, J = 14, 4 Hz), 4.65 (1H, singlet), 3.97 (1H, broad singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 1.93 (3H, singlet), 1.65 (3H, singlet), 1.62 (3H, singlet), 1.29 (3H, singlet), 0.97 (3H, triplet, J = 7.3 Hz ), 0.84 (3H, doublet, J = 6.5 Hz), 0.83 (3H, doublet, J = 6.4 Hz).

Example 11
13- [1- (4-Aminophenyl) cyclopropanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₂ , R ³ = 4-NH ₂ , n = 0 (compound N 388)]
Mass spectrum (FAB-MS) m / z: 731 (M + H ⁺ , M = C ₄₂ H ₅₄ N ₂ O ₉ ).

 Nuclear Magnetic Resonance Spectrum (270 MHz) δ ppm: 7.11 (2H, doublet, J = 8.2 Hz), 6.63 (2H, doublet, J = 8.2 Hz), 4.85 (1H doublet, J = 10.6 Hz), 4.74 and 4.67 (2H, AB quartet, J = 14.8 Hz), 4.65 (1H, singlet), 3.92 (1H, singlet) 3.68 (2H, broad singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, triplet doublet, J = 2.2 and 9.2 Hz), 1.93 (3H, singlet), 1.39 (3H, singlet), 1.12 (2H, multiplet), 0.97 (3H, triplet, J = 7.3 Hz), 0.91 (3H, doublet , J = 6.5 Hz), 0.83 (3H, doublet, J = 6.4 Hz).

Example 12
13- [1- (4-Aminophenyl) cyclobutanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₃ , R ³ = 4-NH ₂ , n = 0 (compound N 452)]
Nuclear Magnetic Resonance Spectrum (270 MHz) δ ppm: 7.19 (2H, doublet, J = 8.1 Hz), 7.01 (2H, doublet, J = 8.1 Hz), 5.96-5 , 71 (3H, multiplet), 5.50-5.25 (3H, multiplet), 4.82 (1H, doublet, J = 10.5 Hz), 4.66 (1H, singlet), 3.57 ( 1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, doublet of triplets, J = 2.2 and 9.2 Hz), 1.96 (3H, singlet), 1.40 (3H, singlet), 0.98 (3H, triplet, J = 7.2 Hz), 0.89 (3H, doublet, J = 6.5 Hz), 0.82 (3H, doublet, J = 6.5 Hz).

Example 13
13- [2- (4-Aminophenyl) -2-methylpropyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CH ₂ , Z => C (Me) ₂ , R ³ = 4- NH ₂ n = 0 (compound N 514)]
Nuclear Magnetic Resonance Spectrum (270 MHz) δ ppm: 7.14 (2H, doublet, J = 8 Hz), 6.63 (2H, doublet, J = 8.5 Hz), 5.90-5, 71 (3H, multiplet), 5.46-5.27 (3H, multiplet), 4.65 (1H, singlet), 3.94 (1H, singlet), 3.22 (1H, doublet, J = 8, 9 Hz).

Example 14
13- [2- (4-Methoxycarbonylaminoacetylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4 -NHCOCH ₂ HCOOMe, n = 0 (compound N 81)]
3.61 g (5.0 mmol) of 13- [2- (4-aminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ , 1.012 g (10.0 mmol) of triethylamine and 2.56 g (10.0 mmol) of 2-chloro-1-methylpyridinium iodide was added in the indicated order to a solution of 2.0 g (15.0 mmol) of N-methoxycarbonyl-glycine in 20 ml of methylene chloride. This mixture was stirred for 1.5 hours at room temperature. After this time, the reaction mixture was poured into water and extracted with ethyl acetate. The extract was dried over anhydrous magnesium sulfate and condensed by evaporation under reduced pressure. The obtained residue was purified by silica gel column chromatography using a mixture of ethyl acetate and hexane with a volume ratio of 6: 4 as eluent, whereby 3.53 g (84.4% yield) of the title compound was obtained.

 Nuclear Magnetic Resonance Spectrum (270 MHz) δ ppm: 8.30 (1H, broad singlet), 7.96 (1H, broad singlet), 7.45 (2H, doublet, J = Hz), 7.24 ( 2H doublet, J = 8.5 Hz), 5.89-5.71 (3H, multiplet), 5.51-5.26 (4H, multiplet), 4.86 (1H, doublet, J = 10.8 Hz), 4.73 and 4.65 (2H, AB quartet, J = 15.0 Hz), 3.99 (1H, doublet, J = 5.6 Hz), 3.97 (3H, singlet), 3.36 (1H, multiplet); 3.75 (3H, singlet).

Examples 15 and 16
In accordance with the procedure described in example 14, the compounds of examples 15 and 16 were obtained using 13- [2- (4-aminophenyl) -2-methylpropyloxy] -5-hydroxyiminomylbemycin A ₄ (prepared as described in example 13).

Example 15
13- [2- (4-Methoxycarbonylaminoacetylaminophenyl) -2-methylpropyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CH ₂ , Z => C (Me) ₂ , R ³ = 4-NHCOCH ₂ NHCOOMe, n = 0 (compound N 547)]
Mass spectrum (FAB-MS) m / z: 983 (M + H ⁺ + triethanolamine = 833 + 1 +149).

 Nuclear Magnetic Resonance Spectrum (270 MHz) δ ppm: 7.88 (1H, broad singlet), 7.80 (1H, broad singlet), 7.42 (2H, doublet, J = 8.9 Hz), 7 31 (2H, doublet, J = 8.9 Hz), 5.85-5.69 (3H, multiplet), 5.45-5.26 (3H, multiplet), 5.12 (1H, multiplet), 4.70 (2H, multiplet), 4.66 (1H, singlet), 3.98 (2H, doublet, J = 5.9 Hz), 3.90 (1H, singlet), 3.74 (3H, singlet) ), 3.57 (1H, broad singlet), 3.36 (1H, triplet, J = 2.4 Hz), 3.25 (1H, doublet, J = 8.9 Hz), 3.13-3, 04 (3H, multiplet).

Example 16
13- {2- [4- (1-Methoxycarbonylpyrrolidine-2-carbonylamino) phenyl] -2-methylpropoxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CH ₂ , Z => C (Me) ₂ , R ³ = 4-NHCO (1-COOMe-2-pyrrolidinyl), n = 0 (compound N 553)]
Mass spectrum (FAB-MS) m / z: 1023 (M + H ⁺ + triethanolamine = 873 + 1 + 149).

 Nuclear Magnetic Resonance Spectrum (270 MHz) δ ppm: 7.89 (1H, broad singlet), 7.44 (2H, doublet, J = 8.5 Hz), 7.30 (2H, doublet, J = 8 5 Hz), 5.85-5.69 (3H, multiplet), 5.44-5.27 (3H, multiplet), 5.14 (1H, multiplet), 4.75 (2H, multiplet), 4 66 (1H, singlet), 4.47 (1H, broad singlet), 3.91 (1H, singlet), 3.77 (3H, singlet), 3.73-3.38 (5H, multiplet), 3 37 (1H, triplet, J = 2.4 Hz), 3.25 (1H, doublet, J = 8.7 Hz), 3.14-3.04 (3H, multiplet).

Example 17
13- [1- (4-Acetylaminophenyl) cyclopropanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₂ , R ³ = 4-NHAc, n = 0 (compound N 392)]
A solution of 0.0121 ml (0.15 mmol) of pyridine in 1.0 ml of methylene chloride and a solution of 0.0142 ml (0.15 mmol) of acetic anhydride in 1.0 ml of methylene chloride were added to a solution of 98.0 mg (0.134 mmol) 13 - [1- (4-aminophenyl) cyclopropanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ (prepared as described in Example 11) in 1.0 ml of methylene chloride at 4 ^° C. This mixture was stirred for 30 minutes at this temperature, and then 10 minutes at room temperature. After this time, the reaction solution was diluted with 15 ml of ethyl acetate, washed three times with water and dried over anhydrous sodium sulfate. The solvent was removed by distillation under reduced pressure. The obtained residue was purified by silica gel column chromatography using a mixture of ethyl acetate and hexane with a volume ratio of 6: 4 as eluent, whereby 70.0 mg (yield 67.6%) of the title compound was obtained.

Mass spectrum (FAB-MS) m / z: 773 (M + H ⁺ , M = C ₄₄ H ₅₆ N ₂ O ₁₀ ).

 Nuclear Magnetic Resonance Spectrum (270 MHz) δ ppm: 8.26 (1H, singlet), 7.43 (2H, doublet, J = 8.4 Hz), 28 (2H, doublet, J = 8.4 Hz ), 5.90-5.73 (3H, multiplet), 5.44-5.27 (3H, multiplet), 4.87 (1H, doublet, J = 10.6 Hz), 4.73 and 4, 67 (2H, AB-quartet, J = 14.4 Hz), 4.65 (1H, singlet), 3.93 (1H, singlet), 3.56 (1H, multiplet), 3.35 (1H, multiplet ), 3.04 (1H, doublet of doublets, J = 2.2 & 9.2 Hz), 2.18 (3H, singlet), 1.93 (3H, singlet), 1.37 (3H, singlet), 0.97 (1H, triplet, J = 7.3 Hz), 0.91 (3H, doublet, J = 6.5 Hz), 0.83 (3H, doublet, J = 6.5 Hz).

Example 18
13- [2- (4-Methanesulfonylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHSO ₂ Me, n = 0 (compound N 148)]
18 (a) 13- [2- (4-Nitrophenyl) -2-methylpropionyloxy] -5-tert-butyldimethylsilyloxyiminomylbemycin A ₄
245 mg (3.6 mmol) of imidazole, 543 mg (3.6 mmol) of tert-butyldimethylsilyl chloride and 20 mg of 4-dimethylaminopyridine were added to a solution of 2.289 g (3.0 mmol) of 13- [2- (4-nitrophenyl) -2 -methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ (prepared as described in Example 1) in 25 ml of methylene chloride and this mixture was stirred at 40 ^° C. for 2 hours. After this time, the reaction mixture was diluted with 100 ml of ethyl acetate, washed successively with 0.2 M aqueous citric acid, water, 4% (w / v) aqueous sodium bicarbonate and again with water, after which it was dried over anhydrous sodium sulfate and the solvent was removed by evaporation under reduced pressure. The resulting residue was purified by silica gel column chromatography using ethyl acetate and hexane mixtures with a volume ratio of 1: 9 as eluent, which afforded 2.542 g (96.6% yield) of the title compound as an amorphous solid.

18 (b) 13- [2- (4-Aminophenyl) -2-methylpropionyloxy] -5-butyldimethylsilyloxyiminomylbemycin A ₄
2.45 g (2.71 mmol) of 13- [2- (4-nitrophenyl) -2-methylpropionyloxy] -5-tert-butyldimethylsilyloxyiminomylbemycin A ₄ [prepared as described in (a) above] was dissolved in 15 ml methanol and 253 mg of bis (triphenylphosphine) -nickel (II) chloride was added to the resulting solution. 170 mg of sodium borohydride was added to this mixture with stirring over 10 minutes and stirring continued for another 7 blinks. The reaction mixture was then poured into 200 ml of a 1% (by weight to volume) aqueous solution of acetic acid and extracted with ethyl acetate, first in an amount of 200 ml, and then 50 ml. The extract was washed successively with water, 4% aqueous sodium bicarbonate and again with water, and then dried over anhydrous sodium sulfate and the solvent was removed by evaporation under reduced pressure. The resulting residue was purified by silica gel column chromatography using a mixture of ethyl acetate and hexane with a volume ratio of 3: 7 as eluent, whereby 2.101 g (91.5% yield) of the title compound was obtained as an amorphous solid.

18 (s)
13- [2- (4-Methanesulfonylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ 0.177 ml (2.20 mmol) of pyridine and 252 mg (2.20 mmol) of methanesulfonyl chloride were added to the solution 169 mg (0, 20 mmol) 13- [2- (4-aminophenyl) -2-methylpropionyloxy] -5-tert-butyldimethylsilyloxyiminomylbemycin A ₄ [prepared as described in (b) above] in 2.0 ml of methylene chloride and the mixture was stirred at room temperature temperature for 2 hours. At the end of this time, the reaction mixture was diluted with 20 ml of ethyl acetate, washed successively with 0.2 M aqueous citric acid solution and water, 4% (w / v) aqueous sodium bicarbonate and again with water, after which it was dried over anhydrous sodium sulfate and the solvent was removed by evaporation under reduced pressure. The residue was diluted in 3.0 ml of methanol, and 0.3 ml of a 1 M aqueous hydrochloric acid solution was added to the resulting solution. Then this mixture was stirred at room temperature for 20 minutes. At the end of this time, the reaction mixture was diluted with 20 ml of ethyl acetate and washed successively with water, 4% (w / v) aqueous sodium bicarbonate and again with water, after which it was dried over anhydrous sodium sulfate. The solvent was removed by evaporation under reduced pressure. The resulting residue was purified by silica gel column chromatography using a mixture of ethyl acetate and hexane with a volume ratio of 6: 4 as eluent, whereby 717 mg (yield 94.5%) of the title compound was obtained as an amorphous solid.

Mass spectrum (FAB-MS) m / z: 811 (M + H ⁺ , M = C ₄₃ H ₅₃ N ₂ O ₁₁ S).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.14 (1H, broad singlet), 7.26 (2H, doublet, J = 8.6 Hz), 7.20 (2H, doublet, J = 8 6 Hz), 6.35 (1H, broad singlet), 4.87 (1H, doublet, J = 9.9 Hz), 4.71 and 4.69 (2H, AB quartet, J = 14.5 Hz), 4.65 (1H, singlet), 3.95 (1H, singlet), 3.56 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 2, 98 (3H, singlet), 1.93 (3H, singlet), 1.58 (3H, singlet), 1.55 (3H, singlet), 1.31 (3H, singlet), 0.98 (3H, triplet , J = 7.3 Hz), 0.84 - 0.80 (6H, multiplet).

Examples 19-56
In accordance with the procedure described in example 18, the compounds were obtained according to examples 19-56.

Example 19
13- [2- (4-Benzoylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOPh , n = 0 (compound N 63)]
Mass spectrum (FAB-MS) m / z: 837 (M + H ⁺ , M = C ₄₉ H ₆₀ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.89-7.31 (2H, multiplet), 7.77 (1H, broad singlet), 7.60-7.47 (5H, multiplet), 7 31 (2H, doublet, J = 8.6 Hz), 4.89 (1H, doublet, J = 10.6 Hz), 4.71 and 4.69 (2H, AB quartet, J = 15.2 Hz), 4.65 (1H, singlet), 3.95 (1H, singlet), 3.56 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 1, 93 (3H, singlet), 1.59 (3H, singlet), 1.56 (3H, singlet), 1.33 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.85-0.82 (6H, multiplet).

Example 20
13- [2- (4-Methoxycarbonylphenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOOMe , n = 0 (compound N 121)]
Mass spectrum (FAB-MS) m / z: 791 (M + H ⁺ , M = C ₄₄ H ₅₈ N ₂ O ₁₁ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.82 (1H, broad singlet), 7.31 (2H, doublet, J = 8.6 Hz), 7.23 (2H, doublet, J = 8 6 Hz), 6.56 (1H, broad singlet), 4.87 (1H, doublet, J = 10.6 Hz), 4.71 and 4.69 (2H, AB quartet, J = 14.5 Hz), 4.65 (1H, singlet), 3.96 (1H, singlet), 3.78 (3H, singlet), 3.56 (1H, multiplet), 3.36 (1H, multiplet), 3, 04 (1H, doublet of triplets, J = 2.6 and 9.2 Hz), 1.93 (3H, singlet), 1.56 (3H, singlet), 1.53 (3H, singlet), 1.30 ( 3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.84 - 0.81 (6H, multiplet).

Example 21
13- {2- [4-Acetylaminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHAc , n = 0 (compound N 26)]
Mass spectrum (FAB-MS) m / z: 775 (M + H ⁺ , M = C ₄₄ H ₅₈ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.83 (1H, broad singlet), 7.42 (2H, doublet, J = 8.6 Hz), 7.25 (2H, doublet, J = 8 6 Hz), 7.11 (1H, broad singlet), 4.87 (1H, doublet, J = 10.6 Hz), 4.71 and 4.69 (2H, AB quartet, J = 14.5 Hz), 4.65 (1H, singlet), 3.95 (1H, singlet), 3.56 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, triplet doublet, J = 2.3 and 9.2 Hz), 2.18 (3H, singlet), 1.93 (3H, singlet), 1.57 (3H, singlet), 1.53 (3H, singlet), 1.30 ( 3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.84-0.80 (6H, multiplet).

Example 22
13- [2- (4-Phenoxycarbonylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOOPh , n = 0 (compound N 131)]
Mass spectrum (FAB-MS) m / z: 853 (M + H ⁺ , M = C ₄₉ H ₆₀ N ₂ O ₁₁ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.89 (1H, broad singlet), 7.43-7.37 (4H, multiplet), 7.29-7.24 (2H, multiplet), 7 , 19 (2H, doublet, J = 7.3 Hz), 6.91 (1H, broad singlet), 4.88 (1H, doublet, J = 10.6 Hz), 4.72 and 4.69 (2H , AB quartet, J = 14.5 Hz), 4.65 (1H, singlet), 3.96 (1H, singlet), 3.56 (1H, multiplet), 3.36 (1H, multiplet), 3 04 (1H, multiplet), 1.93 (3H, singlet), 1.57 (3H, singlet), 1.55 (3H, singlet), 1.31 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (6H, doublet, J = 6.6 Hz).

Example 23
13- [2- (4-Crotonylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOCH = CHMe, n = 0 (compound N 59)]
Mass spectrum (FAB-MS) m / z: 801 (M + H ⁺ , M = C ₄₆ H ₆₀ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.16 (1H, singlet), 7.48 (2H, doublet, J = 8.5 Hz), 7.26 (2H, doublet, J = 8, 5 Hz), 7.11 (1H, singlet), 7.00 (1H, multiplet), 5.93 (1H, doublet of doublets, J = 1.4 & 15.2 Hz), 5.84 (1H, double doublet of doublets, J = 2.0, 2.0 and 11.5 Hz), 4.87 (1H, doublet, J = 10.6 Hz), 4.73 and 4.66 (2H, doublet of AB quartets, J = 1.9 Hz and 14.6 Hz), 4.65 (1H, singlet), 3.97 (1H, singlet), 3.56 (1H, multiplet), 3.36 (1H, multiplet), 3 04 (1H, doublet of triplets, J = 2.0 & 9.4 Hz), 1.93 (3H, singlet), 1.57 (3H, singlet), 1.54 (3H, singlet), 1.30 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (3H, doublet, J = 6.3 Hz), 0.81 (3H, doublet, J = 6, 3 Hz).

Example 24
13- [2- (4-Pivaloylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOtBu , n = 0 (compound N 38)]
Mass spectrum (FAB-MS) m / z: 817 (M + H ⁺ , M = C ₄₇ H ₆₄ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.81 (1H, singlet), 4.88 (1H, doublet, J = 10.6 Hz), 4.72 and 4.69 (2H, AB- quartet, J = 13.9 Hz), 4.65 (1H, singlet), 3.96 (1H, singlet), 3.56 (1H, multiplet), 3.36 (1H, multiplet), 3.04 ( 1H, triplet doublet, J = 2.6 and 9.2 Hz), 1.93 (3H, singlet), 1.57 (3H, singlet), 1.53 (3H, singlet), 1.32 (12H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (6H, doublet, J = 6.3 Hz).

Example 25
13- [2- (4-Valerylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOBu , n = 0 (compound N 36)]
Mass spectrum (FAB-MS) m / z: 817 (M + H ⁺ , M = C ₄₇ H ₆₄ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.90 (1H, broad singlet), 7.44 (2H, doublet, J = 8.6 Hz), 7.24 (2H, doublet, J = 8 , 6 Hz), 7.08 (1H, singlet), 4.87 (1H, doublet, J = 10.6 Hz), 4.72 and 4.69 (2H, AB quartet, J = 15.8 Hz ), 4.65 (1H, singlet), 3.96 (1H, singlet), 3.56 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 1.93 (3H, singlet), 1.57 (3H, singlet), 1.53 (3H, singlet), 1.31 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0 95 (3H, triplet, J = 7.6 Hz); 0.84-0.81 (6H, multiplet).

Example 26
13- {2- [4- (3-Fluorobenzoyl) aminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCO (3-FPh), n = 0 (compound N 65)]
Mass spectrum (FAB-MS) m / z: 855 (M + H ⁺ , M = C ₄₉ H ₅₉ FN ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 9.05 (1H, broad singlet), 7.97 (1H, singlet), 7.65 - 7.56 (2H, multiplet), 7.57 (2H doublet, J = 8.6 Hz), 7.32-7.20 (1H, multiplet), 7.29 (2H, doublet, J = 8.6 Hz), 4.88 (1H, doublet, J = 10.5 Hz), 4.70-4.68 (2H, AB quartet, J = 15.2 Hz), 4.65 (1H, singlet), 4.00 (1H, singlet), 3.56 ( 1H, multiplet), 3.36 (1H, multiplet), 3.05 (1H, multiplet), 1.91 (3H, singlet), 1.58 (3H, singlet), 1.56 (3H, singlet), 1.33 (3H, singlet), 0.98 (3H, triplet, J = 7.2 Hz), 0.83 (6H, doublet, J = 6.6 Hz).

Example 27
13- [2 (4-Methylthioacetylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOCH ₂ SMe, n = 0 (compound N 51)]
Mass spectrum (FAB-MS) m / z: 821 (M + H ⁺ , M = C ₄₅ H ₆₀ N ₂ O ₁₀ S).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.67 (1H, singlet), 8.30 (1H, broad singlet), 7.50 (2H, doublet, J = 8.6 Hz), 7, 28 (2H, doublet, J = 8.6 Hz), 4.88 (1H, doublet, J = 10.5 Hz), 4.72 and 4.69 (2H, AB quartet, J = 14.6 Hz ), 4.66 (1H, singlet), 3.7 (1H, singlet), 3.56 (1H, multiplet), 3.36 (1H, multiplet), 3.35 (2H, singlet), 3.04 (1H, multiplet), 2.05 (3H, singlet), 1.93 (3H, singlet), 1.57 (3H, singlet), 1.55 (3H, singlet), 1.32 (3H, singlet) 0.98 (3H, triplet, J = 7.2 Hz); 0.83 (6H, doublet, J = 6.4 Hz).

Example 28
13- [2- (4-Methoxyacetylaminophenyl) -2-methylpropionyloxy] - 5-hydroxyiminomylbemycin A ₄ [(I) 1 R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOCH ₂ OMe, n = 0 (compound N 47)]
Mass spectrum (FAB-MS) m / z: 805 (M + H ⁺ , M = C ₄₅ H ₆₀ N ₂ O ₁₁ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 9.01 (1H, broad singlet), 8.24 (1H, singlet), 7.51 (2H, doublet, J = 8.6 Hz), 7, 28 (2H, doublet, J = 8.6 Hz), 4.87 (1H, doublet, J = 1.5 Hz), 4.71 and 4.68 (2H, AB quartet, J = 15.2 Hz ), 4.66 (1H, singlet), 3.97 (3H, singlet), 3.58 (1H, multiplet), 3.51 (3H, singlet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 1.92 (3H, singlet), 1.57 (3H, singlet), 1.54 (3H, singlet), 1.30 (3H, singlet), 0.98 (3H, triplet, J = 7.2 Hz), 0.83 (3H, doublet, J = 6.4 Hz), 0.82 (3H, doublet, J = 6.4 Hz).

Example 29
13- [2- (4-Cyclopropylcarbonylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOcPr , n = 0 (compound N 39)]
Mass spectrum (FAB-MS) m / z: 801 (M + H ⁺ , M = C ₄₆ H ₆₀ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.80 (1H, broad singlet), 7.49 (1H, singlet), 7.44 (2H, doublet, J = 8.6 Hz), 7, 24 (2H, doublet, J = 8.6 Hz), 4.87 (1H, doublet, 10.6 Hz), 4.72 and 4.69 (2H, AB quartet, J = 14.8 Hz), 4.66 (1H, singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 1.92 (3H, singlet), 1.56 (3H singlet), 1.53 (3H, singlet), 1.30 (3H, singlet), 1.09 (2H, multiplet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (3H, doublet, J = 6.3 Hz); 0.82 (3H, doublet, J = 6.5 Hz).

Example 30
13- [2- (4-Cyclohexanecarbonylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOcHx , n = 0 (compound N 42)]
Mass spectrum (FAB-MS) m / z: 843 (M + H ⁺ , M = C ₄₉ H ₆₆ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.99 (1H, broad singlet), 7.45 (2H, doublet, J = 8.6 Hz), 7.24 (2H, doublet, J = 8 , 6 Hz), 7.10 (1H, broad singlet), 4.87 (1H, doublet, J = 10.6 Hz), 4.72 and 4.70 (2H, AB quartet, J = 14.5 Hz), 4.65 (1H, singlet), 3.96 (1H, singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 1, 93 (3H, singlet), 1.56 (3H, singlet), 1.53 (3H, singlet), 1.31 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (3H, doublet, J = 6.3 Hz); 0.82 (3H, doublet, J = 6.5 Hz).

Example 31
13- {2- [4- (4-Methoxyphenyl) acetylaminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOCH ₂ (4-MeOPh), n = 0 (compound N 62)]
Mass spectrum (FAB-MS) m / z: 881 (M + H ⁺ , M = C ₅₁ H ₆₄ N ₂ O ₁₁ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.91 (1H, broad singlet), 7.34 (2H, doublet, J = 8.6 Hz), 7.25 (2H, doublet, J = 8 6 Hz), 7.21 (2H, doublet, J = 8.6 Hz), 7.01 (1H, broad singlet), 6.94 (2H, doublet, J = 8.6 Hz), 4.86 (1H, doublet, J = 10.5 Hz), 4.72 and 4.70 (2H, AB quartet, J = 14.3 Hz), 4.66 (1H, singlet), 3.96 (1H, singlet), 3.84 (3H, singlet), 3.69 (2H, singlet), 3.58 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 1, 94 (3H, singlet), 1.54 (3H, singlet), 1.51 (3H, singlet), 1.29 (3H, singlet), 0.98 (3H, triplet, J = 7.2 Hz), 0.82 (6H, doublet, J = 6.6 Hz).

Example 32
13- {2- [4- (4-Nitrobenzoyl) aminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCO (4-NO ₂ Ph), n = 0 (compound N 73)]
Mass spectrum (FAB-MS) m / z: 882 (M + H ⁺ , M = C ₄₉ H ₆₀ N ₃ O ₁₂ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 9.10 (1H, broad singlet), 8.35 (2H, doublet, J = 8.6 Hz), 8.05 (2H, doublet, J = 8 , 6 Hz), 7.82 (1H, singlet), 7.58 (2H, doublet, J = 8.6 Hz), 7.34 (2H, doublet, J = 8.6 Hz), 4.89 ( 1H, doublet, J = 10.6 Hz), 4.74 and 4.66 (2H, AB quartet, J = 15.0 Hz), 4.65 (1H, singlet), 3d, 97 (1H, singlet ), 3.57 (1H, multiplet), 3.35 (1H, multiplet), 3.04 (1H, multiplet), 1.93 (3H, singlet), 1.60 (3H, singlet), 1.57 (3H, singlet), 1.33 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.90-0.80 (4H, multiplet).

Example 33
13- {2- [4- (2-Furoyl) aminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCO (2-furyl), n = 0 (compound N 77)]
Mass spectrum (FAB-MS) m / z: 827 (M + H ⁺ , M = C ₄₇ H ₅₈ N ₂ O ₁₁ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.08 (1H, singlet), 7.59 (2H, doublet, J = 8.6 Hz), 7.51 (1H, doublet, J = 2, 0 Hz), 7.30 (2H, doublet, J = 8.6 Hz), 7.26 (1H, doublet, J = 3.7 Hz), 6.56 (1H, doublet of doublets, J = 2.0 and 3.7 Hz), 4.88 (1H, doublet, J = 10.5 Hz), 4.71 and 4.68 (2H, AB quartet, J = 14.3 Hz), 4.66 (1H singlet), 3.97 (1H, singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 1.92 (3H, singlet), 1 58 (3H, singlet), 1.56 (3H, singlet), 1.31 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (6H, doublet, J = 6.4 Hz).

Example 34
13- [2- (4-Propioloylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOC = CH, n = 0 (compound N 60)]
Mass spectrum (FAB-MS) m / z: 785 (M + H ⁺ , M = C ₄₅ H ₅₆ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.61 (1H, broad singlet), 7.62 (1H, singlet), 7.45 (2H, doublet, J = 8 Hz), 7.27 (2H, doublet, J = 8.6 Hz), 4.87 (1H, doublet, J = 10.5 Hz), 4.71 and 4.69 (2H, AB quartet, J = 14.4 Hz) 4.66 (1H, singlet), 3.98 (1H, broad singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 2.93 (1H, singlet), 1.92 (3H, singlet), 1.57 (3H, singlet), 1.54 (3H, singlet), 1.30 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.84 (3H, doublet, J = 6.4 Hz), 0.83 (3H, doublet, J = 6.5 Hz).

Example 35
13- {2- [4- (4-Nitrophenyl) acetylaminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOCH ₂ (4-NO ₂ Ph), n = 0 (compound N 61)]
Mass spectrum (FAB-MS) m / z: 896 (M + H ⁺ , M = C ₅₀ H ₆₁ N ₃ O ₁₂ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.25 (2H, doublet, J = 8.6 Hz), 7.80 (1H, broad singlet), 7.54 (2H, doublet, J = 8 , 6 Hz), 7.39 (2H, doublet, J = 8.6 Hz), 7.24 (2H, doublet, J = 8.6 Hz), 7.11 (1H, broad singlet), 4.87 (1H, doublet, J = 10.6 Hz), 4.71 and 4.69 (2H, AB quartet, J = 14.1 Hz), 4.65 (1H, singlet), 3.96 (1H, singlet), 3.82 (2H, singlet), 3.58 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, triplet doublet, J = 2.2 and 7.1 Hz) , 1.93 (3H, singlet), 1.56 (3H, singlet), 1.52 (3H, singlet), 1.29 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.84 - 0.80 (6H, multiplet).

Example 36
13- {2- [4- (4-Methoxybenzoyl) aminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCO (4-MeOPh), n = 0 (compound N 69)]
Mass spectrum (FAB-MS) m / z: 867 (M + H ⁺ , M = C ₅₀ H ₆₂ N ₂ O ₁₁ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.85 (2H, doublet, J = 8.8 Hz), 7.70 (1H, broad singlet), 7.57 (2H, doublet, J = 8 , 7 Hz), 7.30 (2H, doublet, J = 8.7 Hz), 6.98 (2H, doublet, J = 8.8 Hz), 4.88 (1H, doublet, J = 10.4 Hz), 4.72 and 4.70 (2H, AB quartet, J = 14.6 Hz), 4.65 (1H, singlet), 3.96 (1H, singlet), 3.88 (3H, singlet ), 3.57 (1H, multiplet), 3.35 (1H, multiplet), 3.04 (1H, triplet doublet, J = 2.4 and 9.1 Hz), 1.93 (3H, singlet), 1.59 (3H, singlet), 1.56 (3H, singlet), 1.32 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (6H, doublet , J = 6.3 Hz).

Example 37
13- {2- [4- (4-Butylbenzoyl) aminophenyl] -2-methylpropionyloxy-5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCO (4-tBuPh), n = 0 (compound N 72)]
Mass spectrum (FAB-MS) m / z: 893 (M + H ⁺ , M = C ₅₃ H ₆₈ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.81 (2H, doublet, J = 8.4 Hz), 7.76 (1H, broad singlet), 7.58 (2H, doublet, J = 8 , 6 Hz), 7.51 (2H, doublet, J = 8.4 Hz), 7.31 (2H, doublet, J = 8.6 Hz), 4.89 (1H, doublet, J = 10.4 Hz), 4.72 and 4.70 (2H, AB quartet, J = 14.8 Hz), 4.65 (1H, singlet), 3.97 (1H, singlet), 3.56 (1H, multiplet ), 3.35 (1H, multiplet), 3.04 (1H, multiplet), 1.93 (3H, singlet), 1.58 (3H, singlet), 1.56 (3H, singlet), 1.36 (9H, singlet), 1.33 (3H, singlet), 0.99 (3H, triplet, J = 7.2 Hz), 0.78 (6H, doublet, J = 6.3 Hz).

Example 38
13- {2- [4- (4-Chlorobenzoyl) aminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCO (4-ClPh), n = 0 (compound N 67)]
Mass spectrum (FAB-MS) m / z: 871 (M + H ⁺ , M = C ₄₉ H ₅₉ ClN ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.94 (1H, broad singlet), 7.83 (2H, doublet, J = 8.5 Hz), 7.74 (1H, wide singlet), 7 57 (2H, doublet, J = 8.6 Hz), 7.48 (2H, doublet, J = 8.5 Hz), 7.32 (2H, doublet, 1 = 8.6 Hz), 4.89 (1H, doublet, J = 10.5 Hz), 4.72 and 4.69 (2H, AB quartet, J = 14.4 Hz), 4.65 (1H, singlet), 3.97 (1H, singlet), 3.56 (1H, multiplet), 3.35 (1H, multiplet), 3.04 (1H, multiplet), 1.93 (3H, singlet), 1.59 (3H, singlet), 1, 56 (3H, singlet), 1.32 (3H, singlet), 0.99 (3H, triplet, J = 7.3 Hz), 0.83 (6H, doublet,] = 6.4 Hz).

Example 39
13- [2- (4-Cyclobutanecarbonylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4 -NHCOcBu, n = 0 (compound N 40)]
Mass spectrum (FAB-MS) m / z: 815 (M + H ⁺ , M = C ₄₇ H ₆₂ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 9.24 (1H, broad singlet), 7.46 (2H, doublet, J = 8.6 Hz), 7.24 (2H, doublet, J = 8 , 6 Hz), 7.20 (1H, singlet), 4.87 (1H, doublet, J = 9.9 Hz), 4.71 and 4.67 (2H, AB quartet, J = 14.9 Hz ), 4.66 (1H, singlet), 3.99 (1H, broad singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.15 (1H, multiplet), 3, 04 (1H, multiplet), 1.91 (3H, singlet), 1.56 (3H, singlet), 1.53 (3H, singlet), 1.30 (3H, singlet), 0.98 (3H, triplet , J = 7.3 Hz), 0.83 (3H, doublet, J = 6.3 Hz), 0.82 (3H, doublet, J = 6.4 Hz).

Example 40
13- [2- (4-Cyclopentanecarbonylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOcPn , n = 0 (compound N 41)]
Mass spectrum (FAB-MS) m / z: 829 (M + H ⁺ , M = C ₄₈ H ₆₄ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.46 (2H, doublet, J = 8.6 Hz), 7.24 (2H, doublet, J = 8.6 Hz), 7.21 (1H singlet), 4.87 (1H, doublet, J = 10.5 Hz), 4.72 and 4.69 (2H, AB quartet, J = 15.3 Hz), 4.66 (1H, singlet) 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 2.67 (1H, multiplet), 1.92 (3H, singlet), 1.56 ( 3H, singlet), 1.53 (3H, singlet), 1.31 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (3H, doublet, J = 6 , 3 Hz), 0.82 (3H, doublet, J = 6.5 Hz).

Example 41
13- [2- (4-Propionylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOEt , n = 0 (compound N 33)]
Mass spectrum (FAB-MS) m / z: 789 (M + H ⁺ , M = C ₄₅ H ₆₀ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 9.09 (1H, broad singlet), 7.45 (2H, doublet, J = 8.6 Hz), 7.24 (2H, doublet, J = 8 , 6 Hz), 4.87 (1H, doublet, J = 10.6 Hz), 4.71 and 4.69 (2H, AB quartet, J = 14.5 Hz), 4.66 (1H, singlet ), 3.98 (1H, broad singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 04 (1H, multiplet), 2.38 (1H, quartet, J = 7.6 Hz), 1.92 (3H, singlet), 1.56 (3H, singlet), 1.53 (3H, singlet), 1.30 (3H, singlet), 0.98 (3H, triplet, J = 7 , 3 Hz), 0.83 (3H, doublet, J = 6.4 Hz), 0.82 (3H, doublet, J = 6.5 Hz).

Example 42
13- [2- (4-Isovalerylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4NHCOiBu, n = 0 (compound N 37)]
Mass spectrum (FAB-MS) m / z: 817 (M + H ⁺ , M = C ₄₇ H ₆₄ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.70 (1H, broad singlet), 7.45 (2H, doublet, J = 8.6 Hz), 7.25 (2H, doublet, J = 8 , 6 Hz), 7.16 (1H, singlet), 4.87 (1H, doublet, J = 10.5 Hz), 4.71 and 4.68 (2H, AB quartet, J = 15.0 Hz ), 4.66 (1H, singlet), 3.88 (1H, broad singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 2, 21 (2H, doublet, J = 2.3 Hz), 1.92 (3H, singlet), 1.56 (3H, singlet), 1.53 (3H, singlet), 1.31 (3H, singlet), 1.02-0.92 (9H, multiplet), 0.83 (3H, doublet, J = 6.6 Hz), 0.82 (3H, doublet, J = 6.3 Hz).

Example 43
13- [2- (4-Isobutyrylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOiPr , n = 0 (compound N 35)]
Mass spectrum (FAB-MS) m / z: 803 (M + H ⁺ , M = C ₄₆ H ₆₂ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 9.20 (1H, broad singlet), 7.45 (2H, doublet, J = 8.6 Hz), 7.31 (1H, singlet), 7, 24 (2H, doublet, J = 86 Hz), 4.87 (1H, doublet, J = 10.5 Hz), 4.71 and 4.69 (2H, AB quartet, J = 15.3 Hz), 4.66 (1H, singlet), 4.01 (1H, broad singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 2.33 ( 1H, multiplet), 1.92 (3H, singlet), 1.56 (3H, singlet), 1.53 (3H, singlet), 1.31 (3H, singlet), 1.03-0.95 (9H multiplet), 0.83 (3H, doublet, J = 6.2 Hz), 0.82 (3H, doublet, J = 6.4 Hz).

Example 44
13- [2- (4-Butyrylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I); R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOPr, n = 0 (compound N 34)]
Mass spectrum (FAB-MS) m / z: 803 (M + H ⁺ , M = C ₄₆ H ₆₂ N ₂ O ₁₀ )
Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 9.35 (1H, broad singlet), 7.45 (2H, doublet, J = 8.6 Hz), 7.35 (1H, singlet), 7, 24 (2H, doublet, J = 8.6 Hz), 4.87 (1H, doublet, J = 10.5 Hz), 4.72 and 4.69 (2H, AB quartet, J = 15.0 Hz ), 4.66 (1H, singlet), 3.99 (1H, broad singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 2, 51 (1H, triplet, J = 6.8 Hz), 1.91 (3H, singlet), 1.56 (3H, singlet), 1.53 (3H, singlet), 1.31 (3H, singlet), 0.98 (3H, triplet, J = 7.2 Hz), 0.83 (3H, doublet, J = 6.3 Hz), 0.82 (3H, doublet, J = 6.5 Hz).

Example 45
13- [2- (4-Bromoacetylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOCH ₂ Br, n = 0 (compound N 43)]
Mass spectrum (FAB-MS) m / z: 853 (M + H ⁺ , M = C ₄₄ H ₅₇ BrN ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.09 (1H, broad singlet), 7.47 (2H, doublet, J = 8.6 Hz), 7.30 (2H, doublet, J = 8 , 6 Hz), 4.88 (1H, doublet, J = 10.7 Hz), 4.72 and 4.69 (2H, AB quartet, J = 14.6 Hz), 4.65 (1H, singlet ), 4.03 (2H, singlet), 3.56 (1H, multiplet), 3.37 (1H, multiplet), 3.04 (1H, triplet doublet, J = 2.0 and 8.9 Hz), 1.93 (3H, singlet), 1.58 (3H, singlet), 1.56 (3H, singlet), 1.31 (3H, singlet), 0.98 (3H, triplet, J = 7.2 Hz ), 0.83-0.74 (6H, multiplet).

Example 46
13- [2- (4-Cyanoacetylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4NHCOCH ₂ CN , n = 0 (compound N 46)]
Mass spectrum (FAB-MS) m / z: 853 (M + H ⁺ , M = C ₄₅ H ₅₇ N ₃ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.69 (1H, broad singlet), 7.44 (2H, doublet, J = 8.6 Hz), 7.30 (2H, doublet, J = 8 , 6 Hz), 4.88 (1H, doublet, J = 10.5 Hz), 4.72 and 4.70 (2H, AB quartet, J = 14.8 Hz), 4.66 (1H, singlet ), 3.57 (1H, multiplet), 3.56 (2H, singlet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 1.93 (3H, singlet), 1.58 (3H, singlet), 1.55 (3H, singlet), 1.31 (3H, singlet), 0.98 (3H, triplet, J = 7.2 Hz), 0.84-0.74 (6H, multiplet).

Example 47
13- {2- [4- (3-Nitrobenzoyl) aminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCO (3-NO ₂ Ph), n = 0 (compound N 74)]
Mass spectrum (FAB-MS) m / z: 871 (M + H ⁺ , M = C ₄₉ H ₅₉ N ₃ O ₁₂ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.71 (1H, singlet), 8.43 (1H, doublet of doublets, J = 1.4 & 8.0 Hz), 8.27 (1H, doublet , J = 8.0 Hz), 7.88 (1H, broad singlet), 7.73 (1H, doublet of doublets, J = 8.0 and 8.0 Hz), 7.60 (2H, doublet, J = 8.6 Hz), 7.35 (2H, doublet, J = 8.6 Hz), 4.90 (1H, doublet, J = 10.5 Hz), 4.72 and 4.69 (2H, AB- quartet, J = 14.4 Hz), 4.65 (1H, singlet), 3.56 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, triplet doublet, J = 2, 2 and 9.7 Hz), 1.93 (3H, singlet), 1.60 (3H, singlet), 1.57 (3H, singlet), 1.33 (3H, singlet), 0.99 (3H, triplet, J = 7.2 Hz), 0.88-0.79 (6H, multiplet).

Example 48
13- {2- [4- (3-Chlorobenzoyl) aminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCO (3-ClPh), n = 0 (compound N 68)]
Mass spectrum (FAB-MS) m / z: 871 (M + H ⁺ M = C ₄₉ H ₅₉ ClN ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.87-7.85 (1H, multiplet), 7.76-7.70 (2H, multiplet), 7.57 (2H, doublet, J = 8 , 6 Hz), 7.44 (1H, doublet of doublets, J = 7.8 and 7.8 Hz), 7.32 (2H, doublet, J = 8.6 Hz), 4.89 (1H, doublet, J = 10.5 Hz), 4.71 and 4.69 (2H, AB quartet, J = 14.2 Hz), 4.65 (1H, singlet), 3.56 (1H, multiplet), 3, 36 (1H, multiplet), 3.04 (1H, multiplet), 1.93 (3H, singlet), 1.59 (3H, singlet), 1.56 (3H, singlet), 1.32 (3H, singlet) ), 0.98 (3H, triplet, J = 7.3 Hz), 0.84-0.77 (6H, multiplet).

Example 49
13- {2- [4- (4-Fluorobenzoyl) aminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCO (4-FPh), n = 0 (compound N 66)]
Mass spectrum (FAB-MS) m / z: 855 (M + H ⁺ , M = C ₄₉ H ₅₉ FN ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.90 (2H, doublet, J = 8.5 Hz), 72 (1H, broad singlet), 7.57 (2H, doublet, J = 86 Hz) , 7.32 (1H, doublet, J = 7.6 Hz), 7.18 (2H, doublet, J = 8.5 Hz), 4.89 (1H, doublet, J = 10.5 Hz), 4 , 72 and 4.69 (2H, AB quartet, J = 14.4 Hz), 4.65 (1H, singlet), 3.56 (1H, multiplet), 3.36 (1H, multiplet), 3, 04 (1H, doublet of triplets, J = 1.9 and 8.9 Hz), 1.93 (3H, singlet), 1.59 (3H, singlet), 1.56 (3H, singlet), 1.32 ( 3H, singlet), 0.98 (3H, triplet, J = 7.2 Hz), 0.83 (6H, doublet, J = 6.3 Hz).

Example 50
13- {2- [4- (2-Fluorobenzoyl) aminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCO (2-FPh), n = 0 (compound N 64)]
Mass spectrum (FAB-MS) m / z: 855 (M + H ⁺ , M = C ₄₉ H ₅₉ FN ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.61 (2H, doublet, J = 8.6 Hz), 7.31 (1H, doublet, J = 7.6 Hz), 4.89 (1H doublet, J = 10.5 Hz), 4.72 and 4.69 (2H, AB quartet, J = 14.4 Hz), 4.65 (1H, singlet), 3.56 (1H, multiplet) , 3.36 (1H, multiplet), 3.04 (1H, multiplet), 1.93 (3H, singlet), 1.59 (3H, singlet), 1.56 (3H, singlet), 1.32 ( 3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (6H, doublet, J = 6.3 Hz).

Example 51
13- [2- (4-Trifluoroacetylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOCF ₃ , n = 0 (compound N 44)]
Mass spectrum (FAB-MS) m / z: 829 (M + H ⁺ , M = C ₄₄ H ₅₅ F ₃ N ₂ O ₁₀ )
Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.81 (1H, broad singlet), 8.03 (1H, singlet), 7.51 (2H, doublet, J = 8.7 Hz), 7, 33 (2H, doublet, J = 8.7), 4.8 (1H, doublet, J = 10.5 Hz), 4.71 and 4.68 (2H, AB quartet, J = 14.2 Hz) 4.65 (1H, singlet), 3.98 (1H, broad singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 1.92 (3H, singlet), 1.58 (3H, singlet), 1.56 (3H, singlet), 1.31 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0 83 (6H, doublet, J = 6.4 Hz).

Example 52
13- [2- (4-Difluoroacetylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOCHF ₂ , n = 0 (compound N 45)]
Mass spectrum (FAB-MS) m / z: 811 (M + H ⁺ , M = C ₄₄ H ₅₆ F ₂ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.72 (1H, broad singlet), 7.93 (1H, singlet), 7.52 (2H, doublet, J = 8.7 Hz), 7, 31 (2H, doublet, J = 8.7 Hz), 6.02 (1H, triplet, J = 54.6 Hz), 4.88 (1H, doublet, J = 10.5 Hz), 4.71 and 4.69 (2H, AB quartet, J = 15.2 Hz), 4.65 (1H, singlet), 3.98 (1H, broad singlet), 3.57 (1H, multiplet), 3.36 ( 1H, multiplet), 3.04 (1H, multiplet), 1.92 (3H, singlet), 1.58 (3H, singlet), 1.55 (3H, singlet), 1.30 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (3H, doublet, J = 6.4 Hz), 0.82 (3H, doublet, J = 6.5 Hz).

Example 53
13- {2- [4- (3-Methoxybenzoyl) aminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCO (3-MeOPh), n = 0 (compound N 70)]
Mass spectrum (FAB-MS) m / z: 867 (M + H ⁺ , M = C ₅₀ H ₆₂ N ₂ O ₁₁ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.05 (1H, broad singlet), 7.78 (1H, singlet), 7.58 (2H, doublet, J = 8.6 Hz), 7, 44 (1H, doublet, J = 1.4 Hz), 7.34-7.41 (2H, multiplet), 7.31 (2H, doublet, J = 8.6 Hz), 7.09 (1H, multiplet ), 4.88 (1H, doublet, J = 10.5 Hz), 4.72 and 4.69 (2H, AB quartet, J = 14.5 Hz), 4.65 (1H, singlet), 3 96 (1H, singlet), 3.88 (3H, singlet), 3.57 (1H, multiplet), 3.35 (1H, multiplet), 3.04 (1H, triplet doublet, J = 2.0 and 9.3 Hz), 1.93 (3H, singlet), 1.59 (3H, singlet), 1.56 (3H, singlet), 1.32 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (6H, doublet, J = 5.8 Hz).

Example 54
13- [2- (4-Tenoylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCO (2-thienyl), n = 0 (compound N 78)]
Mass spectrum (FAB-MS) m / z: 843 (M + H ⁺ , M = C ₄₇ H ₅₈ N ₂ O ₁₀ S).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.09 (1H, singlet), 7.66 (1H, singlet), 7.62 (1H, multiplet), 7.55 (2H, doublet, J = 8.7 Hz), 7.55 (1H, doublet of doublets, J = 2.0 & 4.2 Hz), 7.30 (2H, doublet, J = 8.7 Hz), 7.14 (1H, doublet doublets, J = 4.2 and 4.2 Hz), 5.84 (1H, doublet of doublets of doublets, J = 2.1, 2.1 and 11.5 Hz), 5.78 (1H, multiplet), 4 88 (1H, doublet, J = 10.4 Hz), 4.73 and 4.67 (2H, doublet of AB quartets, J = 2.0 and 14.5 Hz), 4.65 (1H, singlet) , 3.97 (1H, singlet), 3.56 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, triplet doublet, J = 2.3 and 9.3 Hz), 1 93 (3H, doublet, J = 1.4 Hz), 1.59 (3H, singlet), 1.56 (3H, singlet), 1.31 (3H, singlet), 0.98 (3H, triplet, J = 7.2 Hz), 0.83 (6H, d Bletea, J = 6,5 Hz).

Example 55
13- [2- (4-Nicotinoylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCO (3-pyridyl), n = 0 (compound N 75)]
Mass spectrum (FAB-MS) m / z: 838 (M + H ⁺ , M = C ₄₈ H ₅₉ N ₃ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ δ ppm: 9.09 (1H, singlet), 8.78 (1H, doublet, J = 4.8 Hz), 8.6 (1H, singlet), 8.23 ( 1H, doublet, J = 7.9 Hz), 7.91 (1H, singlet), 7.58 (2H, doublet, J = 8.6 Hz), 7.46 (1H, doublet of doublets, J = 4, 8 and 7.9 Hz), 7.33 (2H, doublet, J = 8.6 Hz), 4.89 (1H, doublet, J = 10.6 Hz), 4.73 and 4.67 (2H, doublet of AB quartets, J = 2.0 and 14.7 Hz), 4.66 (1H, singlet), 4.02 (1H, singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, doublet of triplets, J = 2.2 and 9.3 Hz), 1.92 (3H, doublet, J = 1.5 Hz), 1.59 (3H, singlet), 1 56 (3H, singlet), 1.33 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (6H, doublet, J = 6.6 Hz).

Example 56
13- [2- (4-Isonicotinoylaminophenyl) -2-methylpropionyloxy] - 5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCO (4-pyridyl), n = 0 (compound N 76)]
Mass spectrum (FAB-MS) m / z: 838 (M + H ⁺ , M = C ₄₈ H ₅₉ N ₃ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.81 (2H, doublet, J = 5.7 Hz), 8.52 (1H, singlet), 7.88 (1H, singlet), 7.72 (2H, doublet, J = 5.7 Hz), 7.58 (2H, doublet, J = 8.6 Hz), 7.33 (2H, doublet, J = 8.6 Hz), 4.86 (1H doublet, J = 10.5 Hz), 4.73 and 4.67 (2H, doublet of AB quartets, J = 2.0 and 13.5 Hz), 4.66 (1H, singlet), 3.99 (1H, singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, triplet doublet, J = 2.2 and 9.3 Hz), 1.93 (3H singlet), 1.59 (3H, singlet), 1.57 (3H, singlet), 1.32 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (6H, doublet, J = 6.5 Hz).

Example 57
13- [1- (4-Aminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NH ₂ , n = 0 (compound N 171)]
57 (a) 13- [1 (4-Nitrophenyl) cyclopentanecarbonyloxy] -5-oxomylbemycin A ₄
4.11 g (17.5 mmol) of 1- (4-nitrophenyl) cyclopentanecarboxylic acid, 2.0 g of anhydrous copper (II) sulfate and 8 drops of trifluoromethanesulfonic acid were added to the solution of 1.95 g (3.50 mmol) 15-hydroxy-5-oxomylbemycin A ₄ in 50 ml of methylene chloride and the mixture was stirred at room temperature under nitrogen for 20 minutes. After this time, the reaction mixture was filtered to remove insoluble matter, after which the filtrate was poured with stirring into a mixture of 4% (by weight to volume) aqueous solution of sodium bicarbonate and ethyl acetate. The ethyl acetate layer was separated from the mixture, and the aqueous layer was extracted with a small amount of ethyl acetate. The separated ethyl acetate layer was combined with the ethyl acetate extract and the mixture was washed with a 4% (w / v) aqueous solution of sodium bicarbonate and then with water. It was then dried over anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure. The resulting residue was used in the next step without further purification.

57 (b) 13- [1- (4-Nitrophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄
The crude 13- [2- (4-nitrophenyl) cyclopentanecarbonyloxy] -5-oxomylbemycin A ₄ [prepared as described in (a) above] was dissolved in 20 ml of dioxane and 10 ml of water, 20 ml of methanol were added to the resulting solution, and 3.0 g of hydroxylamine hydrochloride. This mixture was stirred at 55 ^° C. for 1 hour, after which it was diluted with ethyl acetate and washed twice with water. After that, the solvent was removed by evaporation under reduced pressure. The resulting residue was used in the next step without further purification.

57 (c) 13- [1- (4-Nitrophenyl) cyclopentanecarbonyloxy] -5-tert-butyldimethylsilyloxyiminomylbemycin A ₄
The crude 13- [1 - (4-nitrophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [prepared as described in (b) above] was dissolved in 30 ml of methylene chloride and 286 mg (4.2 mmol) was added to the resulting solution. imidazole, 634 mg (4.2 mmol) of tert-butyldimethylsilyl chloride and 20 mg of 4-dimethylaminopyridine. This mixture was stirred at 40 ^° C. for 2 hours. At the end of this time, the reaction mixture was diluted with 200 ml of ethyl acetate and washed successively with 0.2 M aqueous citric acid solution, water, 4% (w / v) aqueous sodium bicarbonate and again with water, after which it was dried over anhydrous sodium sulfate . The solvent was removed by evaporation under reduced pressure. The resulting residue was purified by silica gel column chromatography using a mixture of ethyl acetate and hexane with a volume ratio of 1: 9 as eluent, whereby 2.327 g (73.6% yield) of the title compound was obtained as an amorphous solid.

57 (d) 13- [1- (4-aminophenyl) cyclopentanecarbonyloxy] -5-tert-butyldimethylsilyloxyiminomylbemycin A ₄
13- [1- (4-nitrophenyl) cyclopentanecarbonyloxy] -5-tert-butyldimethylsilyloxyiminomylbemycin A ₄ [prepared as described in paragraph (c) above] was dissolved in 15 ml of methanol and 327 mg of bis (triphenylphosphine) was added to the resulting solution - Nickel (II). After that, 230 mg of sodium borohydride was added with stirring over 10 minutes and stirring was continued for another 7 minutes. After this time, the reaction mixture was poured into 200 ml of a 1% (in terms of weight to volume) aqueous solution of acetic acid and was extracted first with 200 ml and then with 50 ml of ethyl acetate. The extract was washed successively with water, 4% (w / v) aqueous sodium bicarbonate and again with water, after which it was dried over anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure. The resulting residue was purified by silica gel column chromatography using a mixture of ethyl acetate and hexane with a volume ratio of 3: 7 as eluent, whereby 1.834 g (81.5% yield) of the title compound was obtained as an amorphous solid.

57 (e) 13- [1- (4-aminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄
873 mg (1.0 mmol) of 13- [1- (4-aminophenyl) cyclopentanecarbonyloxy] -5-tert-butyldimethylsilyloxyiminomylbemycin A ₄ [prepared as described above in paragraph ((d)] was dissolved in 20 ml of methanol and the resulting 2.0 ml of a 1 M aqueous solution of hydrochloric acid was added to the solution, and this mixture was stirred at room temperature for 20 minutes, after which time the reaction mixture was diluted with ethyl acetate and washed successively with water, 4% (w / v) aqueous sodium bicarbonate solution and again with water. Then it was dried over anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure, and the obtained residue was purified by silica gel column chromatography using an ethyl acetate / hexane mixture with a 6: 4 volume ratio as an eluent, whereby 717 mg was obtained (yield 94.5 %) of the title compound as an amorphous solid.

Mass spectrum (FAB-MS) m / z: 759 (M + H ⁺ , M = C ₄₄ H ₅₈ N ₂ O ₉ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.59 (1H, broad singlet), 7.11 (2H, doublet, J = 8.5 Hz), 6.60 (2H, doublet, J = 8 5 Hz), 4.80 (1H, doublet, J = 10.5 Hz), 4.65 (1H, singlet), 3.90 (2H, wide singlet), 3.55 (1H, multiplet), 3 36 (1H, multiplet), 3.02 (1H, doublet of triplets, J = 2.1 and 9.3 Hz), 2.60 (2H, multiplet), 1.93 (3H, singlet), 1.31 (3H, singlet), 0.97 (3H, triplet, J = 7.3 Hz), 0.82 (3H, doublet, J = 6.4 Hz), 0.77 (3H, doublet, J = 6, 5 Hz).

Example 58
13- [2- (4-Methylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHMe , n = 0 (compound N 9)]
The title compound was prepared according to the method described in Example 57, except that 2- [4- (N-nitrobenzyloxycarbonyl) methylaminophenyl] -2-methylpropionic acid was used instead of 1- (4-nitrophenyl) cyclopentanecarboxylic acid.

Mass spectrum (FAB-MS) m / z: 747 (M + H ⁺ , M = C ₄₃ H ₅₈ N ₂ O ₉ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.13 (1H, broad singlet), 7.12 (2H, doublet, J = 8.6 Hz), 7.54 (2H, doublet, J = 8 , 6 Hz), 5.86 (1H, doublet of doublets of doublets, J = 2.1, 2.1 & 11.2 Hz), 5.79 (1H, multiplet), 5.77 (1H, doublet of doublets, J = 11.2 and 14.0 Hz), 4.86 (1H, doublet, J = 10.4 Hz), 4.74 and 4.71 (2H, doublet of AB quartets, 2.1 and 14.5 Hz ), 4.65 (1H, singlet), 3.97 (1H, broad singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, triplet doublet, J = 2.3 and 9.4 Hz), 2.82 (3H, singlet), 1.93 (3H, doublet, J = 1.4 Hz), 1.54 (3H, singlet), 1.51 (3H, singlet), 1.32 (3H, singlet), 0.98 (3H, triplet, J = 7.2 Hz), 0.83 (6H, doublet, J = 6.5 Hz).

Example 59
13- [1- (4-Acetylaminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHAc, n = 0 (compound N 191)]
1.31 g (1.50 mmol) of 13- [1- (4-aminophenyl) cyclopentanecarbonyl] -5-tert-butyldimethylsilyloxyiminomylbemycin A ₄ [prepared as described in Example 57 (c)] was dissolved in 15 ml of methylene chloride and 0.137 ml (1.70 mmol) of pyridine and 0.161 ml (1.70 mmol) of acetic anhydride were added to the resulting solution. This mixture was stirred at room temperature for 20 minutes. After this time, the reaction mixture was diluted with 100 ml of ethyl acetate and washed successively with 0.2 M aqueous citric acid solution, water, 4% (in terms of weight to volume) aqueous sodium bicarbonate solution and again with water. Then it was dried over anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure. The residue was dissolved in 30 ml of methanol, and 3.0 ml of a 1 M aqueous solution of hydrochloric acid was added to the resulting solution. The reaction mixture was stirred at room temperature for 20 minutes, diluted with ethyl acetate, and then washed successively with water, 4% (w / v) aqueous sodium bicarbonate and again with water. The mixture was then dried over anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure. The resulting residue was purified by silica gel column chromatography using a mixture of ethyl acetate and hexane with a volume ratio of 6: 4 as eluent, whereby 717 mg (yield 94.5%) of the title compound was obtained as an amorphous solid.

Mass spectrum (FAB-MS) m / z: 801 (M + H ⁺ , M = C ₄₄ H ₆₀ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.34 (1H, singlet), 7.41 (2H, doublet, J = 8.5 Hz), 7.28 (2H, doublet, J = 8, 5 Hz), 7.17 (1H, singlet), 5.83 (1H, multiplet), 5.78 (1H, multiplet), 5.77 (1H, multiplet), 4.80 (1H, doublet, J = 10.5 Hz), 4.74 and 4.60 (2H, doublet of AB quartets, J = 1.9 and 14.6 Hz), 4.65 (1H, singlet), 3.97 (1H, singlet) 3.54 (1H, multiplet), 3.36 (1H, multiplet), 3.02 (1H, doublet of triplets, J = 2.2 and 9.3 Hz), 2.61 (2H, multiplet), 2 , 17 (3H, singlet), 1.93 (3H, singlet), 1.29 (3H, singlet), 0.97 (3H, triplet, J = 7.3 Hz), 0.82 (3H, doublet, J = 6.5 Hz), 0.76 (3H, doublet, J = 6.5 Hz).

Examples 60-71
The compounds of examples 60-71 were obtained in accordance with the procedures described in example 59.

Example 60
13- [1- (4-Methanesulfonylaminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHSO ₂ Me , n = 0 (compound N 313)]
Mass spectrum (FAB-MS) m / z: 837 (M + H ⁺ , M = C ₄₅ H ₆₀ N ₂ O ₁₁ S).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ δ ppm: 8.74 (1H, broad singlet), 7.32 (2H, doublet, J = 8.6 Hz), 7.14 (2H, doublet, J = 8, 6 Hz), 6.72 (1H, broad singlet), 4.80 (1H, doublet, J = 10.6 Hz), 4.73 and 4.60 (2H, AB quartet, J = 14.5 Hz ), 4.65 (1H, singlet), 3.99 (1H, singlet), 3.54 (1H, multiplet), 3.36 (1H, multiplet), 3.01 (1H, doublet of triplets, J = 2 , 2 and 9.3 Hz), 2.96 (3H, singlet), 2.61 (2H, multiplet), 1.91 (3H, singlet), 1.28 (3H, singlet), 0.96 (3H triplet, J = 7.2 Hz), 0.81 (3H, doublet, J = 6.3 Hz), 0.74 (3H, doublet, J = 6.5 Hz).

Example 61
13- [1- (4-Pivaloylaminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHCOtBu, n = 0 (compound N 203)]
Mass spectrum (FAB-MS) m / z: 843 (M + H ⁺ , M = C ₄₉ H ₆₆ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.50 (1H, broad singlet), 7.44 (2H, doublet, J = 8.7 Hz), 7.20-7.30 (3H, multiplet ), 4.81 (1H, doublet, J = 10.5 Hz), 4.75 and 4.67 (2H, AB quartet, J = 14.5 Hz), 4.65 (1H, singlet), 3 96 (1H, broad singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 2.59 (2H, multiplet), 1.92 (3H, singlet), 1.31 (3H singlet), 1.14 (3H, doublet, J = 5.9 Hz), 1.02 (3H, doublet, J = 6.4 Hz), 0.82 (3H, doublet, J = 6.4 Hz )

Example 62
13- [1- (4-Cyclohexanecarbonylaminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHCO-cHx , n = 0 (compound N 207)]
Mass spectrum (FAB-MS) m / z: 869 (M + H ⁺ , M = C ₅₁ H ₆₈ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.57 (1H, broad singlet), 7.44 (2H, doublet, J = 8.6 Hz), 7.27 (2H, doublet, J = 8 , 6 Hz), 7.17 (1H, singlet), 4.81 (1H, doublet, J = 10.6 Hz), 4.74 and 4.66 (2H, AB quartet, J = 15.2 Hz ), 4.66 (1H, singlet), 4.00 (1H, broad singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 3.02 (1H, multiplet), 2, 59 (2H, multiplet), 1.92 (3H, singlet), 1.30 (3H, singlet), 0.97 (3H, triplet, J = 7.3 Hz), 0.82 (3H, doublet, J = 6.4 Hz), 0.76 (3H, doublet, J = 6.5 Hz).

Example 63
13- [1- (4-Valerylaminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHCOBu, n = 0 (compound N 201)]
Mass spectrum (FAB-MS) m / z: 843 (M + H ⁺ , M = C ₄₉ H ₆₆ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.30 (1H, broad singlet), 7.43 (2H, doublet, J = 8.5 Hz), 7.27 (2H, doublet, J = 8 5 Hz), 7.08 (1H, singlet), 4.81 (1H, doublet, J = 10.6 Hz), 4.75 and 4.67 (2H, AB quartet, J = 15.0 Hz ), 4.66 (1H, singlet), 3.95 (1H, broad singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 3.02 (1H, multiplet), 2, 60 (2H, multiplet), 1.93 (3H, singlet), 1.31 (3H, singlet), 1.00-0.90 (4H, multiplet), 0.82 (3H, doublet, J = 6, 4 Hz), 0.76 (3H, doublet, J = 6.5 Hz).

Example 64
13- [1- (4-Propionylaminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHCOEt, n = 0 (compound N 198)]
Mass spectrum (FAB-MS) m / z: 815 (M + H ⁺ , M = C ₄₇ H ₆₂ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.50 (1H, broad singlet), 7.43 (2H, doublet, J = 8.5 Hz), 7.27 (2H, doublet, J = 8 5 Hz), 7.12 (1H, broad singlet), 4.81 (1H, doublet, J = 10.5 Hz), 4.74 and 4.66 (2H, AB quartet, J = 15.2 Hz), 4.65 (1H, singlet), 3.95 (1H, broad singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 3.02 (1H, multiplet), 2 60 (2H, multiplet), 1.92 (3H, singlet), 1.30 (3H, singlet), 0.97 (3H, triplet, J = 7.2 Hz), 0.82 (3H, doublet, J = 6.3 Hz), 0.76 (3H, doublet, J = 6.5 Hz).

Example 65
13- [1- (4-Cyclopropanecarbonylaminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHCOcPr, n = 0 (compound N 204)]
Mass spectrum (FAB-MS) m / z: 827 (M + H ⁺ , M = C ₄₈ H ₆₂ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.11 (1H, broad singlet), 7.52-7.28 (5H, multiplet), 4.80 (1H, doublet, J = 10.4 Hz ), 4.75 and 4.68 (2H, doublet of AB quartets, J = 1.8 and 14.9 Hz), 4.65 (1H, singlet), 3.97 (1H, broad singlet), 3, 55 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, multiplet), 2.62 (2H, multiplet), 1.93 (3H, singlet), 1.29 (3H, singlet) ), 0.97 (3H, triplet, J = 7.2 Hz), 0.82 (3H, doublet, J = 6.4 Hz), 0.76 (3H, doublet, J = 6.5 Hz).

Example 66
13- {1- [4- (Cyclobutanecarbonylamino) phenyl] cyclopentanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4- NHCOcBu, n = 0 (compound N 205)]
Mass spectrum (FAB-MS) m / z: 843 (M + H ⁺ , M = C ₄₉ H ₆₄ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ / ppm: 8.13 (1H, singlet), 7.44 (2H, doublet, J = 8.7 Hz), 7.27 (2H, doublet, J = 8 , 7 Hz), 6.97 (1H, singlet), 4.81 (1H, doublet, J = 10.4 Hz), 4.74 and 4.68 (2H, AB quartet, J = 14.4 Hz ), 4.65 (1H, singlet), 3.97 (1H, singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 3.02 (1H, multiplet), 2.58 (2H, multiplet), 1.93 (3H, singlet), 1.30 (3H, singlet), 0.97 (3H, triplet, J = 7.2 Hz), 0.82 (3H, doublet, J = 6.4 Hz), 0.76 (3H, doublet, J = 6.5 Hz).

Example 67
13- [1- (4-Cyanoacetylaminophenyl) cyclopentanecarbonyloxy] - 5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHCOCH ₂ CN , n = 0 (compound N 211)]
Mass spectrum (FAB-MS) m / z: 826 (M + H ⁺ , M = C ₄₇ H ₅₉ N ₃ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.07 (1H, singlet), 7.70 (1H, singlet), 7.42 (2H, doublet, J = 8.7 Hz), 7.33 (2H, doublet, J = 8.7 Hz), 4.81 (1H, doublet, J = 10.4 Hz), 4.74 and 4.68 (2H, AB quartet, J = 14.4 Hz) 4.65 (1H, singlet), 3.97 (1H, singlet), 3.55 (2H, singlet), 3.54 (1H, multiplet), 3.36 (1H, multiplet), 3.02 ( 1H, multiplet), 2.61 (2H, multiplet), 1.93 (3H, doublet, J = 1.6 Hz), 1.30 (3H, singlet), 0.97 (3H, triplet, J = 7 , 2 Hz), 0.82 (3H, doublet, J = 6.5 Hz), 0.76 (3H, doublet, J = 6.5 Hz).

Example 68
13- [1- (4-Butyrylaminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHCOPr, n = 0 (compound N 199)]
Mass spectrum (FAB-MS) m / z: 829 (M + H ⁺ , M = C ₄₈ H ₆₄ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.12 (1H, singlet), 7.43 (2H, doublet, J = 8.6. Hz), 7.28 (2H, doublet, J = 8 , 6 Hz), 7.09 (1H, singlet), 4.81 (1H, doublet, J = 10.4 Hz), 4.74 and 4.67 (2H, doublet of AB quartets, J = 2.0 and 14.4 Hz), 4.65 (1H, singlet), 3.97 (1H, singlet), 3.54 (1H, multiplet), 3.36 (1H, multiplet), 3.02 (1H, multiplet ), 2.61 (2H, multiplet), 1.93 (3H, doublet, J = 1.6 Hz), 1.30 (3H, singlet), 1.03-0.95 (6H, multiplet), 0 82 (3H, doublet, J = 6.4 Hz); 0.76 (3H, doublet, J = 6.4 Hz).

Example 69
13- [1- (4-Isobutyrylaminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I); R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHCOiPr, n = 0 (compound N 200)]
Mass spectrum (FAB-MS) m / z: 829 (M + H ⁺ , M = C ₄₈ H ₆₄ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.11 (1H, singlet), 7.44 (2H, doublet, J = 8.6 Hz), 7.28 (2H, doublet, J = 8, 6 Hz), 7.10 (1H, singlet), 4.81 (1H, doublet, J = 10.4 Hz), 4.75 and 4.68 (2H, AB quartet doublet, J = 2.0 and 14.4 Hz), 4.65 (1H, singlet), 3.97 (1H, singlet), 3.54 (1H, multiplet), 3.36 (1H, multiplet), 3.02 (1H, multiplet) 2.60 (2H, multiplet), 1.93 (3H, doublet, J = 1.6 Hz), 1.30 (3H, singlet), 1.26 (6H, doublet, J = 6.8 Hz) , 0.97 (3H, triplet, J = 7.2 Hz), 0.82 (3H, doublet, J = 6.4 Hz), 0.77 (3H, doublet, J = 6.4 Hz).

Example 70
13- [1- (4-Isovalerylaminophenyl) cyclopentanecarbonyloxy] - 5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHCOiBu, n = 0 (compound N 202)]
Mass spectrum (FAB-MS) m / z: 843 (M + H ⁺ , M = C ₄₉ H ₆₆ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.14 (1H, broad singlet), 7.43 (2H, doublet, J = 8.6 Hz), 7.28 (2H, doublet, J = 8 , 6 Hz), 7.07 (1H, singlet), 4.81 (1H, doublet, J = 10.4 Hz), 4.74 and 4.68 (2H, doublet of AB quartets, J = 1.8 and 14.2 Hz), 4.65 (1H, singlet), 3.97 (1H, singlet), 3.54 (1H, multiplet), 3.36 (1H, multiplet), 3.01 (1H, multiplet ), 2.60 (2H, multiplet), 1.93 (3H, doublet, J = 1.4 Hz), 1.30 (3H, singlet), 1.02 (6H, doublet, J = 7.2 Hz ), 0.97 (3H, triplet, J = 7.2 Hz), 0.82 (3H, doublet, J = 6.4 Hz), 0.76 (3H, doublet, J = 6.4 Hz).

Example 71
13- {1- [4- (Cyclopentanecarbonylamino) phenyl] cyclopentanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4- NHCOcPn, n = 0 (compound N 206)]
Mass spectrum (FAB-MS) m / z: 855 (M + H ⁺ , M = C ₅₀ H ₆₆ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.16 (1H, broad singlet), 7.44 (2H, doublet, J = 8.4 Hz), 7.27 (2H, doublet, J = 8 , 4 Hz), 7.12 (1H, singlet), 4.81 (1H, doublet, J = 10.8 Hz), 4.74 and 4.68 (2H, doublet of AB quartets, J = 1.8 and 14.2 Hz), 4.65 (1H, singlet), 3.97 (1H, singlet), 3.54 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, multiplet ), 2.66 (1H, multiplet), 2.61 (2H, multiplet), 1.93 (3H, doublet, J = 1.4 Hz), 1.30 (3H, singlet), 0.97 (3H triplet, J = 7.3 Hz), 0.82 (3H, doublet, J = 6.4 Hz), 0.76 (3H, doublet, J = 6.4 Hz).

Example 72
13 {-2- [4- (N-Methylmethanesulfonylamino) phenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-N (Me) SO ₂ Me, n = 0 (compound N 151)]
Mass spectrum (FAB-MS) m / z: 825 (M + H ⁺ , M = C ₄₄ H ₆₀ N ₂ O ₁₁ S).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.05 (1H, singlet), 7.31 (4H, singlet), 4.87 (1H, doublet, J = 10.7 Hz), 4.73 and 4.67 (2H, doublet of AB quartets, J = 2.0 and 14.3 Hz), 4.65 (1H, singlet), 3.96 (1H, singlet), 3.57 (1H, multiplet) , 3.36 (1H, multiplet), 3.30 (3H, singlet), 3.03 (1H, doublet of doublets, J = 2.3 & 9.3 Hz), 2.81 (3H, singlet), 1 , 93 (3H, singlet), 1.59 (3H, singlet), 1.56 (3H, singlet), 1.29 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz) 0.83 (3H, doublet, J = 6.6 Hz); 0.81 (3H, doublet, J = 6.6 Hz).

Example 73
13- {2- [4- (N-Methylmethoxycarbonylamino) phenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4N (Me) COOMe, n = 0 (compound N 123)]
Mass spectrum (FAB-MS) m / z: 805 (M + H ⁺ , M = C ₄₅ H ₆₀ N ₂ O ₁₁ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.10 (1H, singlet), 7.27 (2H, doublet, J = 8.5 Hz), 7.16 (2H, doublet, J = 8, 5 Hz), 4.87 (1H, doublet, J = 10.6 Hz), 4.73 and 4.67 (2H, doublet of AB quartets, J = 2.0 and 14.5 Hz), 4.65 (1H, singlet), 3.97 (1H, singlet), 3.71 (3H, singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.27 (3H, singlet) , 3.03 (1H, doublet of doublets, J = 2.2 & 9.3 Hz), 1.93 (3H, singlet), 1.59 (3H, singlet), 1.56 (3H, singlet), 1 , 29 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (3H, doublet, J = 6.5 Hz), 0.81 (3H, doublet, J = 6.5 Hz).

Examples 74-83
The compounds of Examples 74-83 were prepared from 13- [1- (4-nitro-phenyl) cyclobutanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ (prepared as described in Example 7) in accordance with the procedures described in Example 18.

Example 74
13- [1- (4-Acetylaminophenyl) cyclobutanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₃ , R ³ = 4-NHAc, n = 0 (compound N 457)]
Mass spectrum (FAB-MS) m / z: 787 (M + H ⁺ , M = C ₄₅ H ₅₈ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.34 (1H, singlet), 7.41 (2H, doublet, J = 8.5 Hz), 7.28 (2H, doublet, J = 8, 5 Hz), 7.17 (1H, singlet), 5.83 (1H, multiplet), 5.78 (1H, multiplet), 5.77 (1H, multiplet), 4.80 (1H, doublet, J = 10.5 Hz), 4.74 and 4.60 (2H, doublet of AB quartets, J = 1.9 and 14.6 Hz), 4.65 (1H, singlet), 3.97 (1H, singlet) 3.54 (1H, multiplet), 3.36 (1H, multiplet), 3.02 (1H, doublet of triplets, J = 2.2 and 9.3 Hz), 2.61 (2H, multiplet), 2 , 17 (3H, singlet), 1.93 (3H, singlet), 1.29 (3H, singlet), 0.97 (3H, triplet, J = 7.3 Hz), 0.82 (3H, doublet, J = 6.5 Hz), 0.76 (3H, doublet, J = 6.5 Hz).

Example 75
13- [1- (4-Methoxycarbonylaminophenyl) cyclobutanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₃ , R ³ = 4-NHCOOMe, n = 0 (compound N 491)]
Mass spectrum (FAB-MS) m / z: 803 (M + H ⁺ , M = C ₄₅ H ₅₈ N ₂ O ₁₁ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.82 (1H, broad singlet), 7.32 (2H, doublet, J = 8.6 Hz), 7.21 (2H, doublet, J = 8 6 Hz), 6.57 (1H, wide singlet), 4.84 (1H, doublet, J = 10.6 Hz), 4.72 and 4.70 (2H, AB quartet, J = 14.5 Hz), 4.65 (1H, singlet), 3.95 (1H, singlet), 3.78 (3H, singlet), 3.54 (1H, multiplet), 3.36 (1H, multiplet), 3, 03 (1H, doublet of triplets, J = 2.3 & 9.2 Hz), 2.86-2.70 (2H, multiplet), 2.52-2.41 (3H, multiplet), 1.93 (3H singlet), 1.34 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.82 (3H, doublet, J = 6.6 Hz), 0.76 (3H doublet, J = 6.6 Hz).

Example 76
13- [1- (4-Methanesulfonylaminophenyl) cyclobutanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₃ , R ³ = 4-NHSO ₂ Me , n = 0 (compound N 503)]
Mass spectrum (FAB-MS) m / z: 823 (M + H ⁺ , M = C ₄₄ H ₅₈ N ₂ O ₁₁ S).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.85 (1H, broad singlet), 7.27 (2H, doublet, J = 8.6 Hz), 6.35 (1H, wide singlet), 4 85 (1H, doublet, J = 10.6 Hz), 4.73 and 4.70 (2H, AB quartet, J = 14.5 Hz), 4.66 (1H, singlet), 3.96 ( 1H, singlet), 3.54 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, multiplet), 2.98 (3H, singlet), 2.88 - 2.73 (2H multiplet), 2.53-2.42 (3H, multiplet), 1.93 (3H, singlet), 1.34 (3H, singlet), 0.97 (3H, triplet, J = 7.3 Hz) 0.82 (3H, doublet, J = 6.4 Hz); 0.76 (3H, doublet, J = 6.6 Hz).

Example 77
13- {1- [4- (4-Nitrobenzoylamino) phenyl] cyclobutanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₃ , R ³ = 4-NHCO (4-NO ₂ Ph), n = 0 (compound N 478)]
Mass spectrum (FAB-MS) m / z: 894 (M + H ⁺ , M = C ₅₀ H ₅₉ N ₃ O ₁₂ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.60 (1H, broad singlet), 8.35 (2H, doublet, J = 8.8 Hz), 8.05 (2H, doublet, J = 8 , 4 Hz), 7.85 (1H, singlet), 7.59 (2H, doublet, J = 8.4 Hz), 7.31 (2H, doublet, J = 8.8 Hz), 4.87 ( 1H, doublet, J = 10.4 Hz), 4.74 and 4.68 (2H, doublet of AB quartets, J = 1.6 and 14.4 Hz), 4.65 (1H, singlet), 3, 96 (1H, singlet), 3.54 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, multiplet), 2.88 - 2.75 (2H, multiplet), 1.93 (3H, singlet), 1.36 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.82 (3H, doublet, J = 6.4 Hz), 0.79 (3H, doublet, J = 6.4 Hz).

Example 78
13 {1- [4- (4-tert-Butylbenzoylamino) phenyl] cyclobutanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₃ , R ³ = 4-NHCO (4-tBuPh), n = 0 (compound N 479)]
Mass spectrum (FAB-MS) m / z: 905 (M + H ⁺ , M = C ₅₄ H ₆₈ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.02 (1H, broad singlet), 7.81 (2H, doublet, J = 8.4 Hz), 7.77 (1H, singlet), 7, 59 (2H, doublet, J = 8.4 Hz), 7.50 (2H, doublet, J = 8.4 Hz), 7.29 (1H, singlet), 4.86 (1H, doublet, J = 10 , 4 Hz), 4.75 and 4.68 (2H, AB quartet, J = 14.7 Hz), 4.66 (1H, singlet), 3.95 (1H, singlet), 3.55 (1H multiplet), 3.36 (1H, multiplet), 3.03 (1H, multiplet), 2.87 - 2.74 (2H, multiplet), 1.93 (3H, singlet), 1.36 (12H, multiplet), 0.98 (3H, triplet, J = 7.4 Hz), 0.82 (3H, doublet, J = 6.4 Hz), 0.78 (3H, doublet, J = 6.8 Hz) .

Example 79
13- {1- [4- (4-Methoxybenzoylamino) phenyl] cyclobutanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₃ , R ³ = 4-NHCO (4-MeOPh), n = 0 (compound N 476)]
Mass spectrum (FAB-MS) m / z: 867 (M + H ⁺ , M = C ₅₀ H ₆₂ N ₂ O ₁₁ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.23 (1H, broad singlet), 7.85 (2H, doublet, J = 8.8 Hz), 7.73 (1H, singlet), 7, 58 (2H, doublet, J = 8.6 Hz), 7.28 (1H, singlet), 6.98 (2H, doublet, J = 8.8 Hz), 4.86 (1H, doublet, J = 10 4 Hz), 4.75 and 4.68 (2H, oak-years of AB quartets, J = 1.8 and 14.6 Hz), 4.66 (1H, singlet), 3.95 (1H, singlet ), 3.88 (3H, singlet), 3.54 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, multiplet), 2.87 - 2.74 (2H, multiplet) , 1.93 (3H, singlet), 1.36 (3H, multiplet), 0.98 (3H, triplet, J = 7.4 Hz), 0.82 (3H, doublet, J = 6.6 Hz) 0.78 (3H, doublet, J = 6.4 Hz).

Example 80
13- {1- [4- (4-Chlorobenzoylamino) phenyl] cyclobutanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₃ , R ³ = 4NHCO (4-ClPh), n = 0 (compound N 477)]
Mass spectrum (FAB-MS) m / z: 883 (M + H ⁺ , M = C ₅₀ H ₅₉ ClN ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.04 (1H, broad singlet), 7.82 (2H, doublet, J = 8.8 Hz), 7.76 (1H, singlet), 7, 57 (2H, doublet, J = 8.4 Hz), 7.47 (2H, doublet, J = 8.4 Hz), 7.28 (2H, doublet, J = 8.8 Hz), 4.86 ( 1H, doublet, J = 10.4 Hz), 4.75 and 4.68 (2H, doublet of AB quartets, J = 1.8 and 14.6 Hz), 4.66 (1H, singlet), 3, 96 (1H, singlet), 3.54 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, multiplet), 2.87 - 2.74 (2H, multiplet), 1.93 (3H, singlet), 1.36 (3H, singlet), 0.98 (3H, triplet, J = 7.2 Hz), 0.82 (3H, doublet, J = 6.4 Hz), 0.78 (3H, doublet, J = 6.4 Hz).

Example 81
13- [1- (4-Valerylaminophenyl) cyclobutanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₃ , R ³ = 4-NHCOBu, n = 0 (compound N 461)]
Mass spectrum (FAB-MS) m / z: 829 (M + H ⁺ , M = C ₄₈ H ₆₄ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.48 (1H, broad singlet), 7.46 (2H, doublet, J = 8.6 Hz), 7.22 (2H, doublet, J = 8 , 6 Hz), 7.11 (1H, singlet), 4.85 (1H, doublet, J = 10.4 Hz), 4.75 and 4.68 (2H, doublet of AB quartets, J = 1.6 and 14.4 Hz), 4.66 (1H, singlet), 3.96 (1H, singlet), 3.54 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, multiplet ), 2.84 - 2.72 (2H, multiplet), 1.93 (3H, singlet), 1.34 (3H, singlet), 0.99 - 0.93 (6H, multiplet), 0.82 ( 3H, doublet, J = 6.4 Hz), 0.77 (3H, doublet, J = 6.4 Hz).

Example 82
13- [1- (4-Pivaloylaminophenyl) cyclobutanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₃ , R ³ = 4-NHCOtBu, n = 0 (compound N 462)]
Mass spectrum (FAB-MS) m / z: 829 (M + H ⁺ , M = C ₄₈ H ₆₄ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.09 (1H, broad singlet), 7.47 (2H, doublet, J = 8.8 Hz), 7.29 (1H, singlet), 7, 23 (2H, doublet, J = 8.8 Hz), 4.85 (1H, doublet, J = 10.8 Hz), 4.75 and 4.68 (2H, doublet of AB quartets, J = 1.8 and 14.2 Hz), 4.66 (1H, singlet), 3.95 (1H, singlet), 3.54 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, multiplet ), 2.85 - 2.72 (2H, multiplet), 1.93 (3H, singlet), 1.34 (3H, singlet), 1.32 (9H, singlet), 0.98 (3H, triplet, J = 7.4 Hz), 0.82 (3H, doublet, J = 6.8 Hz), 0.78 (3H, doublet, J = 6.4 Hz).

Example 83
13- {1- [4- (Cyclohexanecarbonylamino) phenyl] cyclobutanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₃ , R ³ = 4- NHCOcHx, n = 0 (compound N 464)]
Mass spectrum (FAB-MS) m / z: 855 (M + H ⁺ , M = C ₅₀ H ₆₆ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.20 (1H, broad singlet), 7.47 (2H, doublet, J = 8.6 Hz), 7.22 (2H, doublet, J = 8 6 Hz), 7.12 (1H, singlet), 4.85 (1H, doublet, J = 10.4 Hz), 4.75 and 4.68 (2H, doublet of AB quartets, J = 1.8 and 14.2 Hz), 4.66 (1H, singlet), 3.95 (1H, singlet), 3.54 (1H, multiplet), 3.36 (1H, multiplet), 3.05 (1H, multiplet ), 2.85 - 2.71 (2H, multiplet), 1.93 (3H, singlet), 1.34 (3H, singlet), 0.97 (3H, triplet, J = 7.2 Hz), 0 82 (3H, doublet, J = 6.4 Hz); 0.77 (3H, doublet, J = 6.4 Hz).

Example 84
13- [1- (4-Aminophenyl) -1-ethylbutyryloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Et) ₂ , R ³ = 4-NH ₂ , n = 0 (compound N 332)] 84 (a) 13- [1- (4-Aminophenyl) -1-ethylbutyryloxy] -5-tert-butyldi-methylsilyloxyiminomylbemycin A ₄
15-Hydroxy-5-oxomylbemycin was treated with 1- (4-nitrophenyl) -1-ethylbutyric acid under the conditions described in example 57 (a), the resulting substance was treated in the same manner as described in example 57 (b), (c ) and (d), whereby the title compound was obtained as an amorphous solid, the yield of which was 46.9%.

84 (b) 13- [1- (4-aminophenyl) -1-ethylbutyryloxy] -5-hydroxyiminomylbemycin A ₄
The title compound was prepared from 13- [1 - (4-aminophenyl) -1-ethylbutyryloxy] -5-tert-butyldimethylsilyloxyiminomylbemycin A ₄ [prepared as described above in (a)] in accordance with the procedures described in Example 57 (e).

Mass spectrum (FAB-MS) m / z: 761 (M + H ⁺ , M = C ₄₄ H ₆₀ N ₂ O ₉ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.84 (1H, singlet), 6.99 (2H, doublet, J = 8.6 Hz), 6.61 (2H, doublet, J = 8, 6 Hz), 4.88 (1H, doublet, J = 10.7 Hz), 4.73 and 4.67 (2H, doublet of AB quartets, J = 2.2 and 14.4 Hz), 4.65 (1H, singlet), 3.99 (1H, singlet), 3.65-3.50 (3H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, doublet of doublets, J = 2, 2 and 9.4 Hz), 1.93 (3H, doublet, 3 = 1.8 Hz), 1.27 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0 , 83 (3H, doublet, J = 6.1 Hz), 0.82 (3H, doublet, J = 6.4 Hz), 0.72 (3H, triplet, J = 7.4 Hz), 0.67 (3H, triplet, J = 7.4 Hz).

Example 85
13- [1- (4-Acetylaminophenyl) -1-ethylbutyryloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Et) ₂ , R ³ = 4-NHAc , n = 0 (compound N 336)]
172 mg (0.20 mmol) 13- [1- (4-aminophenyl) -1-ethylbutyryloxy] -5-tert-butyldimethylsilyloxyiminomylbemycin A ₄ [prepared as described in Example 84 (a)] was dissolved in 2.0 ml methylene chloride and 0.018 ml (0.22 mmol) of pyridine and 0.021 ml (0.22 mmol) of acetic anhydride were added to the resulting solution. The resulting mixture was stirred at room temperature for 20 minutes. After this time, the reaction mixture was diluted with 20 ml of ethyl acetate and washed successively with 0.2 M aqueous citric acid solution, water, 4% (w / v) aqueous sodium bicarbonate and again with water. Then it was dried over anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure. The resulting residue was dissolved in 4.0 ml of methanol, and 0.4 ml of a 1 M aqueous solution of hydrochloric acid was added to the resulting solution. The reaction mixture was stirred at room temperature for 20 minutes, after which it was diluted with 20 ml of ethyl acetate and washed successively with water, 4% (w / v) aqueous sodium bicarbonate and again with water. Then it was dried over anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure. The resulting residue was purified by silica gel column chromatography using a mixture of ethyl acetate and hexane with a volume ratio of 6: 4 as eluent, whereby 149 mg (yield 92.7%) of the title compound was obtained as an amorphous solid.

Mass spectrum (FAB-MS) m / z: 803 (M + H ⁺ , M = C ₄₆ H ₆₂ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.30 (1H, singlet), 7.42 (2H, doublet, J = 8.6 Hz), 7.17 (2H, doublet, J = 8, 6 Hz), 7.15 (1H, broad singlet), 4.89 (1H, doublet, J = 10.6 Hz), 4.73 and 4.65 (2H, AB quartet, J = 14.3 Hz ), 4.65 (1H, singlet), 3.99 (1H, singlet), 3.58 (1H, multiplet), 3.37 (1H, multiplet), 3.03 (1H, multiplet), 2.17 (3H, singlet), 1.93 (3H, singlet), 1.25 (3H, singlet), 0.98 (3H, triplet, J = 7.1 Hz), 0.84-0.79 (6H, multiplet), 0.72-0.65 (6H, multiplet).

Examples 86-89
The compounds of examples 86-89 were obtained in accordance with the procedures described in example 85.

Example 86
13- [1- (4-Methanesulfonylaminophenyl) -1-ethylbutyryloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Et) ₂ , R ³ = 4-NHSO ₂ Me, n = 0 (compound N 380)]
Mass spectrum (FAB-MS) m / z: 839 (M + H ⁺ , M = C ₄₅ H ₆₂ N ₂ O ₁₁ S).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.15 (1H, singlet), 7.23 (2H, doublet, J = 8.6 Hz), 7.14 (2H, doublet, J = 8, 6 Hz), 6.43 (1H, singlet), 4.89 (1H, doublet, J = 10.6 Hz), 4.73 and 4.65 (2H, AB quartet, J = 15.4 Hz) 4.65 (1H, singlet), 4.00 (1H, singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 2.98 ( 3H, singlet), 1.93 (3H, singlet), 1.27 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (3H, doublet, J = 6 , 6 Hz), 0.79 (3H, doublet, J = 6.0 Hz), 0.75-0.66 (6H, multiplet).

Example 87
13- {1- [4- (4-Chlorobenzoylamino) phenyl] -1-ethylbutyryloxy} - 5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Et) ₂ , R ³ = 4-NHCO (4-ClPh), n = 0 (compound N 356)]
Mass spectrum (FAB-MS) m / z: 899 (M + H ⁺ , M = C ₅₁ H ₆₄ ClN ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.65 (1H, singlet), 7.82 (2H, doublet, J = 8.5 Hz), 7.73 (1H, singlet), 7.56 (2H, doublet, J = 8.6 Hz), 7.48 (2H, doublet, J = 8.5 Hz), 7.24 (2H, doublet, J = 8.7 Hz), 4.91 (1H doublet, J = 10.5 Hz), 4.74 and 4.66 (2H, AB quartet, J = 14.4 Hz), 4.65 (1H, singlet), 4.00 (1H, singlet) , 3.58 (1H, multiplet), 3.35 (1H, multiplet), 3.05 (1H, multiplet), 1.93 (3H, singlet), 1.28 (3H, singlet), 0.99 ( 3H, triplet, J = 7.3 Hz), 0.81-0.84 (6H, multiplet), 0.76-0.66 (6H, multiplet).

Example 88
13- [1- (4-Valerylaminophenyl) -1-ethylbutyryloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Et) ₂ , R ³ = 4-NHCOBu , n = 0 (compound N 342)]
Mass spectrum (FAB-MS) m / z: 845 (M + H ⁺ , M = C ₄₉ H ₆₈ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.34 (1H, broad singlet), 7.43 (2H, doublet, J = 8.6 Hz), 7.17 (2H, doublet, J = 8 , 6 Hz), 7.09 (1H, singlet), 4.90 (1H, doublet, J = 10.8 Hz), 4.73 and 4.65 (2H, doublet of AB quartets, J = 2.2 and 14.6 Hz), 4.65 (1H, singlet), 3.99 (1H, singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet ), 2.20 (1H, doublet of doublets, J = 11.6 & 24.0 Hz), 1.93 (3H, singlet), 1.26 (3H, singlet), 1.00-0.88 (6H multiplet), 0.86-0.77 (6H, multiplet), 0.73-0.66 (6H, multiplet).

Example 89
13- {1- [4- (Cyclohexanecarbonylamino) phenyl] -1-ethylbutyryloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Et) 2, R ³ = 4-NHCOcHx, n = 0 (compound N 345)]
Mass spectrum (FAB-MS) m / z: 871 (M + H ⁺ , M = C ₅₁ H ₇₀ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.05 (1H, broad singlet), 7.45 (2H, doublet, J = 8.6 Hz), 7.16 (2H, doublet, J = 8 , 6 Hz), 7.11 (1H, singlet), 4.90 (1H, doublet, J = 10.8 Hz), 4.73 and 4.65 (2H, doublet of AB quartets, J = 2.0 and 14.4 Hz), 4.65 (1H, singlet), 3.99 (1H, singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet ), 1.93 (3H, singlet), 1.27 (3H, singlet), 0.98 (3H, triplet, J = 7.2 Hz), 0.84-0.80 (6H, multiplet), 0 73-0.67 (6H, multiplet).

Examples 90-97
The compounds of Examples 90-97 were prepared from 13- [1- (4-nitro-phenyl) cyclopropanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ (prepared as described in Example 6) in accordance with the procedures described in Example 18.

Example 90
13- [1- (4-Methanesulfonylaminophenyl) cyclopropanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₂ , R ³ = 4-NHSO ₂ Me , n = 0 (compound N 441)]
Mass spectrum (FAB-MS) m / z: 809 (M + H ⁺ , M = C ₄₃ H ₅₆ N ₂ O ₁₁ S>
Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.13 (1H, singlet), 7.32 (2H, doublet, J = 8.5 Hz), 7.15 (2H, doublet, J = 8, 5 Hz), 6.50 (1H, singlet), 4.88 (1H, doublet, J = 10.4 Hz), 4.73 and 4.70 (2H, doublet of AB quartets, J = 2.0 and 14.5 Hz), 4.65 (1H, singlet), 3.93 (1H, singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, multiplet) 3.01 (3H, singlet), 1.93 (3H, doublet, J = 1.4 Hz), 1.38 (3H, singlet), 1.17 (2H, multiplet), 0.97 (3H, triplet, J = 7.3 Hz), 0.92 (3H, doublet, J = 6.5 Hz), 0.82 (3H, doublet, J = 6.5 Hz).

Example 91
13- [1- (4-Methoxycarbonylaminophenyl) cyclopropanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₂ , R ³ = 4-NHCOOMe, n = 0 (compound N 429)]
Mass spectrum (FAB-MS) m / z: 789 (M + H ⁺ , M = C ₄₄ H ₅₆ N ₂ O ₁₁ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.11 (1H, singlet), 7.31 (2H, doublet, J = 8.4 Hz), 7.26 (2H, doublet, J = 8, 4 Hz), 6.61 (1H, singlet), 4.86 (1H, doublet, J = 10.4 Hz), 4.73 and 4.65 (2H, AB quartet doublet, J = 2.1 and 14.5 Hz), 4.65 (1H, singlet), 3.92 (1H, singlet), 3.78 (3H, singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet) , 3.03 (1H, doublet of triplets, J = 2.2 & 9.3 Hz), 1.93 (3H, singlet), 1.37 (3H, singlet), 1.15 (2H, multiplet), 0 97 (3H, triplet, J = 7.3 Hz), 0.91 (3H, doublet, J = 6.5 Hz), 0.82 (3H, doublet, J = 6.5 Hz).

Example 92
13- [1- (4-Bromoacetylaminophenyl) cyclopropanecarbonyloxy] - 5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₂ , R ³ = 4-NHCOCH ₂ Br , n = 0 (compound N 402)]
Mass spectrum (FAB-MS) m / z: 851 (M + H ⁺ , M = C ₄₄ H ₅₅ BrN ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.14 (1H, singlet), 8.13 (1H, singlet), 7.47 (2H, doublet, J = 8.4 Hz), 7.32 (2H, doublet, J = 8.4 Hz), 4.87 (1H, doublet, J = 10.5 Hz), 4.73 and 4.66 (2H, doublet of AB quartets, J = 2.0 and 15.3 Hz), 4.65 (1H, singlet), 4.04 (2H, singlet), 3.93 (1H, singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet) , 3.03 (1H, doublet of triplets, J = 2.2 and 9.4 Hz), 1.93 (3H, doublet of doublets, J = 1.5 and 1.5 Hz), 1.37 (3H, singlet ), 1.15 (2H, multiplet), 0.97 (3H, triplet, J = 7.3 Hz), 0.91 (3H, doublet, J = 6.5 Hz), 0.83 (3H, doublet , J = 6.5 Hz).

Example 93
13- [1- (4-Isobutoxycarbonylaminophenyl) cyclopropanecarbonyloxy] - 5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₂ , R ³ = 4-NHCOOiBu, n = 0 (compound N 431)]
Mass spectrum (FAB-MS) m / z: 831 (M + H ⁺ , M = C ₄₇ H ₆₂ N ₂ O ₁₁ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.01 (1H, singlet), 7.32 (2H, doublet, J = 8.6 Hz), 7.26 (2H, doublet, J = 8, 6 Hz), 6.60 (1H, singlet), 4.86 (1H, doublet, J = 10.5 Hz), 4.73 and 4.67 (2H, doublet of AB quartets, J = 2.0 and 14.6 Hz), 4.65 (1H, singlet), 3.96 (2H, doublet, J = 6.7 Hz), 3.92 (1H, singlet), 3.55 (1H, multiplet), 3 , 36 (1H, multiplet), 3.03 (1H, doublet of triplets, 3 = 2.2 and 9.4 Hz), 1.93 (3H, singlet), 1.37 (3H, singlet), 1.15 (2H, multiplet), 0.97 (6H, doublet, J = 6.9 Hz), 0.97 (3H, triplet, J = 7.2 Hz), 0.91 (3H, doublet, J = 6, 5 Hz), 0.83 (3H, doublet, J = 6.5 Hz).

Example 94
13- [1- (4-Cyanoacetylaminophenyl) cyclopropanecarbonyloxy] - 5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₂ , R ³ = 4-NHCOCH ₂ CN n = 0 (compound N 401)]
Mass spectrum (FAB-MS) m / z: 798 (M + H ⁺ , M = C ₄₅ H ₅₅ N ₃ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.24 (1H, singlet), 7.80 (1H, singlet), 7.42 (2H, doublet, J = 8.6 Hz), 7.32 (2H, doublet, J = 8.6 Hz), 4.88 (1H, doublet, J = 10.5 Hz), 4.73 and 4.67 (2H, doublet of AB quartets, J = 1.9 and 14.6 Hz), 4.65 (1H, singlet), 3.94 (1H, singlet), 3.55 (1H, multiplet), 3.54 (2H, singlet), 3.36 (1H, multiplet) , 3.03 (1H, doublet of triplets, J = 2.1 and 9.5 Hz), 1.93 (3H, doublet, J = 1.5 Hz), 1.38 (3H, singlet), 1.18 (2H, multiplet), 0.97 (3H, triplet, J = 7.3 Hz), 0.92 (3H, doublet, J = 6.6 Hz), 0.83 (3H, doublet, J = 6, 5 Hz).

Example 95
13- {1- [4- (4-Nitrobenzoylamino) phenyl] cyclopropanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₂ , R ³ = 4-NHCO (4-NO ₂ Ph), n = 0 (compound N 416)]
Mass spectrum (FAB-MS) m / z: 880 (M + H ⁺ , M = C ₄₉ H ₅₈ N ₃ O ₁₂ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.35 (2H, doublet, J = 8.8 Hz), 8.07 (1H, singlet), 8.05 (2H, doublet, J = 8, 8 Hz), 7.88 (1H, singlet), 7.58 (2H, doublet, J = 8.4 Hz), 7.37 (2H, doublet, J = 8.4 Hz), 4.90 (1H doublet, J = 10.4 Hz), 4.73 and 4.66 (2H, doublet of AB quartets, J = 1.9 and 14.4 Hz), 4.64 (1H, singlet), 3.94 (1H, singlet), 3.55 (1H, multiplet), 3.54 (2H, singlet), 3.36 (1H, multiplet), 3.03 (1H, multiplet), 1.93 (3H, singlet) , 1.39 (3H, singlet), 1.18 (2H, multiplet), 0.97 (3H, triplet, J = 7.2 Hz), 0.93 (3H, doublet, J = 6.4 Hz) 0.83 (3H, doublet, J = 6.4 Hz).

Example 96
13- {1- [4- (4-tert-Butylbenzoylamino) phenyl] cyclopropanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₂ , R ³ = 4-NHCO (4-tBuPh), n = 0 (compound N 417)]
Mass spectrum (FAB-MS) m / z: 913 (M + Na ⁺ , M = C ₅₃ H ₆₇ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.08 (1H, broad singlet), 7.81 (2H, doublet, J = 8.8 Hz), 7.79 (1H, singlet), 7, 58 (2H, doublet, J = 8.4 Hz), 7.51 (2H, doublet, J = 8.8 Hz), 7.33 (2H, doublet, J = 8.4 Hz), 4.88 ( 1H, doublet, J = 10.4 Hz), 4.73 and 4.66 (2H, doublet of AB quartets, J = 1.9 and 14.6 Hz), 4.65 (1H, singlet), 3, 92 (1H, singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, multiplet), 1.93 (3H, singlet), 1.38 (3H, singlet) ), 1.18 (2H, multiplet), 0.97 (3H, triplet, J = 7.2 Hz), 0.92 (3H, doublet, J = 6.4 Hz), 0.83 (3H, doublet , J = 6.4 Hz).

Example 97 13- {1- [4- (3,4-Dimethoxybenzoylamino) phenyl] cyclopropanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₂ , R ³ = 4-NHCO (3,4-di-MeOPh), n = 0 (compound N 415)]
Mass spectrum (FAB-MS) m / z: 895 (M + H ⁺ , M = C ₅₁ H ₆₂ N ₂ O ₁₂ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm :. 7.76 (1H, doublet, J = 7.5 Hz), 7.59 (1H, singlet), 7.11 (2H, doublet, J = 7.9 Hz), 6.91 (1H, doublet, J = 8.6 Hz), 6.63 (2H, doublet, J = 8.6 Hz), 4.85 (1H, doublet, J = 10.8 Hz), 4.78-4.64 (2H, multiplet ), 4.68 (1H, singlet), 3.96 (3H, singlet), 3.95 (3H, singlet), 3.55 (1H, multiplet), 3.37 (1H, multiplet), 3.03 (1H, multiplet), 1.95 (3H, singlet), 1.39 (3H, singlet), 1.18 (2H, multiplet), 1.00-0.92 (6H, multiplet), 0.83 ( 3H, doublet, J = 6.6 Hz).

Example 98
13- {2- [4- (3-Methoxycarbonylaminopropionyl) aminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOCH ₂ CH ₂ NHCOOMe, n = 0 (compound N 110)]
0.032 ml (0.30 mmol) of triethylamine and 41 mg (0.31 mmol) of isobutyl chloroformate were added at 4 ^° C to a solution of 44 mg (0.30 mmol) of methoxycarbonylaminopropionic acid in 2.0 ml of methylene chloride and stirred for 5 minutes. To the resulting mixture was added 101 mg (0.12 mmol) of 13- [2- (4-aminophenyl) -2-methylpropionyloxy] -5- tert-butyldimethylsilyloxyiminomylbemycin A ₄ [prepared as described in Example 18 (a) and (b )] and stirred at room temperature for 2 hours. After this time, the reaction mixture was diluted with 20 ml of ethyl acetate and washed successively with 0.2 M aqueous citric acid solution, water, 4% (w / v) aqueous sodium bicarbonate and again with water. Then it was dried over anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure. The resulting residue was dissolved in 2.0 ml of methanol and 0.2 ml of a 1 M aqueous solution of hydrochloric acid was added. The reaction mixture was stirred at room temperature for 20 minutes, after which it was diluted with 20 ml of ethyl acetate and washed successively with water, 4% (w / v) aqueous sodium bicarbonate and again with water. After which it was dried over anhydrous sodium sulfate and the solvent was removed by evaporation under reduced pressure. The resulting residue was purified by silica gel column chromatography using a mixture of ethyl acetate and hexane with a volume ratio of 6: 4 as eluent, which afforded 96 mg (yield 92.8%) of the title compound as an amorphous solid.

Mass spectrum (FAB-MS) m / z: 862 (M + H ⁺ , M = C ₄₇ H ₆₃ N ₃ O ₁₂ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.39 (1H, singlet), 7.50 (1H, singlet), 7.44 (2H, doublet, J = 8.6 Hz), 7.26 (2H, doublet, J = 8.6 Hz), 4.87 (1H, doublet, J = 10.6 Hz), 4.73 and 4.67 (2H, doublet of AB quartets, J = 2.0 and 14.7 Hz), 4.66 (1H, singlet), 3.98 (1H, singlet), 3.78 (3H, singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet) , 3.04 (1H, doublet of triplets, J = 2.2 & 9.3 Hz), 1.93 (3H, singlet), 1.56 (3H, singlet), 1.54 (3H, singlet), 1 , 31 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (3H, doublet, J = 6.0 Hz), 0.82 (3H, doublet, J = 6.3 Hz).

Examples 99-109
The compounds of examples 99-109 were obtained in accordance with the procedures described in example 98.

Example 99 13- {2- [4-N-Methyl-N-methoxycarbonylglycyl) aminophenyl] - 2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C ( Me) ₂ , R ³ = 4-NHCOCH ₂ (Me) COOMe, n = 0 (compound N 95)]
Mass spectrum (FAB-MS) m / z: 862 (M + H ⁺ , M = C ₄₇ H ₆₃ N ₃ O ₁₂ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.22 (1H, singlet), 7.45 (2H, doublet, J = 8.6 Hz), 7.26 (2H, doublet, J = 8, 6 Hz), 4.87 (1H, doublet, J = 10.4 Hz), 4.74 and 4.67 (2H, doublet of AB quartets, J = 2.0 and 14.5 Hz), 4.66 (1H, singlet), 4.03 (2H, singlet), 3.97 (1H, singlet), 3.78 (3H, singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet) , 3.06 (3H, singlet), 3.04 (1H, triplet doublet, J = 2.3 and 9.4 Hz), 1.93 (3H, doublet, J = 1.4 Hz), 1.56 (3H, singlet), 1.53 (3H, singlet), 1.31 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (3H, doublet, J = 6.5 Hz), 0.82 (3H, doublet, J = 6.5 Hz).

Example 100
13- {2- [4- (N-Methoxycarbonylpropyl) aminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCO (1-COOMe-2-pyrrolidinyl), n = 0 (compound N 112)]
Mass spectrum (FAB-MS) m / z: 888 (M + H ⁺ , M = C ₄₉ H ₆₅ N ₃ O ₁₂ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.13 (1H, singlet), 7.46 (2H, doublet, J = 8.6 Hz), 7.24 (2H, doublet, J = 8, 6 Hz), 4.88 (1H, doublet, J = 10.6 Hz), 4.74 and 4.68 (2H, doublet of AB quartets, J = 2.0 and 14.4 Hz), 4.66 (1H, singlet), 3.97 (1H, singlet), 3.78 (3H, singlet), 3.73 (1H, multiplet), 3.57 (1H, multiplet), 3.36 (1H, multiplet) , 3.04 (1H, doublet of triplets, J = 2.3 and 9.3 Hz), 1.93 (3H, doublet, J = 1.5 Hz), 1.56 (3H, singlet), 1.53 (3H, singlet), 1.32 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (6H, doublet, J = 6.5 Hz).

Example 101
13- {2- [4- (N-Methoxycarbonylglycyl) methylaminophenyl] -2-methyl-propionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-N (Me) COCH ₂ NHCOOMe, n = 0 (compound N 96)]
Mass spectrum (FAB-MS) m / z: 862 (M + H ⁺ , M = C ₄₇ H ₆₃ N ₃ O ₁₂ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.12 (1H, singlet), 7.38 (2H, doublet, J = 8.5 Hz), 7.14 (2H, doublet, J = 8, 5 Hz), 4.88 (1H, doublet, J = 10.4 Hz), 4.73 and 4.68 (2H, doublet of AB quartets, J = 1.9 and 14.7 Hz), 4.65 (1H, singlet), 3.97 (1H, singlet), 3.64 (3H, singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.23 (3H, singlet) , 3.04 (1H, doublet of triplets, J = 2.2 and 9.4 Hz), 1.93 (3H, doublet, J = 1.5 Hz), 1.61 (3H, singlet), 1.58 (3H, singlet), 1.31 (3H, singlet), 0.98 (3H, triplet, J = 7.2 Hz), 0.83 (3H, doublet, J = 6.4 Hz), 0.82 (3H, doublet, J = 6.3 Hz).

Example 102
13- {2- [4- (N-tert-butoxycarbonylglycyl) aminophenyl] -2-methyl-propionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me ) ₂ , R ³ = 4-NHCOCH ₂ NHCOOtBu, n = 0 (compound N 89)]
Mass spectrum (FAB-MS) m / z: 890 (M + H ⁺ , M = C ₄₉ H ₆₇ N ₃ O ₁₂ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.19 (1H, singlet), 8.07 (1H, broad singlet), 7.36 (2H, doublet, J = 8.4 Hz), 7, 26 (2H, doublet, J = 8.4 Hz), 4.87 (1H, doublet, J = 10.4 Hz), 4.74 and 4.67 (2H, doublet of AB quartets, J = 1.7 and 14.6 Hz), 4.65 (1H, singlet), 3.97 (1H, singlet), 3.92 (2H, doublet, J = 6.0 Hz), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 1.93 (3H, singlet), 1.60 (3H, singlet), 1.56 (3H, singlet), 1.53 (3H singlet), 1.48 (9H, singlet), 0.98 (3H, triplet, J = 7.4 Hz), 0.83 (6H, doublet, J = 6.5 Hz).

Example 103
13- {2- [4- (N-Methoxycarbonyl-2,2-dimethylglycyl) aminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOC (Me) ₂ NHCOOMe, n = 0 (compound N 107)]
Mass spectrum (FAB-MS) m / z: 874 (M + H ⁺ , M = C ₄₈ H ₆₃ N ₃ O ₁₂ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.67 (1H, broad singlet), 8.17 (1H, singlet), 7.47 (2H, doublet, J = 8.6 Hz), 7, 28 (2H, doublet, J = 8.6 Hz), 5.13 (1H, singlet), 4.87 (1H, doublet, J = 10.4 Hz), 4.74 and 4.67 (2H, doublet AB quartets, J = 1.8 and 14.6 Hz), 4.65 (1H, singlet), 3.92 (1H, singlet), 3.71 (3H, singlet), 3.56 (1H, multiplet ), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 1.93 (3H, singlet), 1.61 (6H, singlet), 1.38 (3H, singlet), 0.98 (3H, triplet, J = 7.4 Hz); 0.83 (6H, doublet, J = 6.5 Hz).

Example 104
13- {1- [4- (N-Metoxycarbonylglycyl) aminophenyl] cyclopropanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₂ , R ³ = 4-NHCOCH ₂ NHCOOMe, n = 0 (compound N 422)]
Mass spectrum (FAB-MS) m / z: 846 (M + H ⁺ , M = C ₄₆ H ₅₉ N ₃ O ₁₂ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.43 (1H, singlet), 8.00 (1H, broad singlet), 7.46 (2H, doublet, J = 8.5 Hz), 7, 29 (2H, doublet, J = 8.5 Hz), 4.87 (1H, doublet, J = 10.4 Hz), 4.73 and 4.67 (2H, doublet of AB quartets, J = 2.0 and 14.7 Hz), 4.66 (1H, singlet), 4.00 (2H, doublet, J = 5.9 Hz), 3.94 (1H, singlet), 3.75 (3H, singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, triplet doublet, J = 2.0 and 9.3 Hz), 1.93 (3H, doublet, J = 1 6 Hz), 1.36 (3H, singlet), 1.15 (2H, multiplet), 0.97 (3H, triplet, J = 7.2 Hz), 0.91 (3H, doublet, J = 6 5Hz), 0.83 (3H, doublet, J = 6.4 Hz).

Example 105
13- {1- [4- (N-Metoxycarbonylglycyl) aminophenyl] cyclobutanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₃ , R ³ = 4-NHCOCH ₂ NHCOOMe, n = 0 (compound N 484)]
Mass spectrum (FAB-MS) m / z: 860 (M + H ⁺ , M = C ₄₇ H ₆₁ N ₃ O ₁₂ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.23 (1H, singlet), 7.94 (1H, broad singlet), 7.46 (2H, doublet, J = 8.4 Hz), 7, 23 (2H, doublet, J = 8.4 Hz), 5.47 (1H, multiplet), 4.84 (1H, doublet, J = 10.4 Hz), 4.75 and 4.68 (2H, doublet AB quartets, J = 1.9 and 14.6 Hz), 4.66 (1H, singlet), 4.00 (2H, doublet, J = 6.0 Hz), 3.96 (1H, singlet), 3.75 (3H, singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, multiplet), 2.84 - 2.73 (2H, multiplet), 1 93 (3H, singlet), 1.33 (3H, singlet), 0.97 (3H, triplet, J = 7.2 Hz), 0.82 (3H, doublet, J = 6.4 Hz), 0 77 (3H, doublet, J = 6.4 Hz).

Example 106
13- {1- [4- (N-Metoxycarbonylglycyl) aminophenyl] cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHCOCH ₂ NHCOOMe, n = 0 (compound N 246)]
Mass spectrum (FAB-MS) m / z: 874 (M + H ⁺ , M = C ₄₈ H ₆₃ N ₃ O ₁₂ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.34 (1H, singlet), 7.96 (1H, broad singlet), 7.43 (2H, doublet, J = 8.4 Hz), 7, 29 (2H, doublet, J = 8.4 Hz), 5.50 (1H, broad singlet), 4.81 (1H, doublet, J = 10.4 Hz), 4.74 and 4.67 (2H, doublet of AB quartets, J = 1.8 and 14.4 Hz), 4.66 (1H, singlet), 3.99 (2H, doublet, J = 6.0 Hz), 3.98 (1H, singlet) , 3.75 (3H, singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, multiplet), 2.64-2.56 (2H, multiplet), 2.17 (1H, doublet of doublets, J = 11.6 & 24.0 Hz), 1.93 (3H, singlet), 1.29 (3H, singlet), 0.97 (3H, triplet, J = 7 , 2 Hz), 0.82 (3H, doublet, J = 6.4 Hz), 0.76 (3H, doublet, J = 6.4 Hz).

Example 107
13- {1- [4- (N-Methoxycarbonyl) -2,2-dimethylglycyl) aminophenyl] cyclopentanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C ( CH ₂ ) ₄ , R ³ = 4-NHCOC (Me) ₂ NHCOOMe, n = 0 (compound N 272)]
Mass spectrum (FAB-MS) m / z: 902 (M + H ⁺ , M = C ₅₀ H ₆₇ N ₃ O ₁₂ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.64 (1H, broad singlet), 7.45 (2H, doublet, J = 8.4 Hz), 7.28 (2H, doublet, J = 8 4 Hz), 5.20 (1H, broad singlet), 4.82 (1H, doublet, J = 10.4 Hz), 4.75 and 4.68 (2H, doublet of AB quartets, J = 1, 8 and 14.2 Hz), 4.66 (1H, singlet), 3.67 (3H, singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, multiplet), 2.65-2.52 (2H, multiplet), 2.18 (1H, doublet of doublets, J = 11.6 and 24.0 Hz), 1.93 (3H, singlet), 1.60 ( 3H, singlet), 1.58 (3H, singlet), 1.32 (3H, singlet), 0.97 (3H, triplet, J = 7.2 Hz), 0.82 (3H, doublet, J = 6 4 Hz), 0.78 (3H, doublet, J = 6.4 Hz).

Example 108
13- {1- [4- (N-Acetylglycyl) aminophenyl] cyclopentanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHCOCH ₂ NHAc, n = 0 (compound N 256)]
Mass spectrum (FAB-MS) m / z: 858 (M + H ⁺ , M = C ₄₈ H ₆₃ N ₃ O ₁₁ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.50 (1H, singlet), 8.45 (1H, broad singlet), 7.45 (2H, doublet, J = 8.6 Hz), 7, 28 (2H, doublet, J = 8.6 Hz), 6.56 (1H, multiplet), 4.80 (1H, doublet, J = 10.4 Hz), 4.74 and 4.67 (2H, doublet AB quartets, J = 1.8 and 14.6 Hz), 4.10 (2H, doublet, J = 5.2 Hz), 4.00 (1H, singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, multiplet), 2.64-2.56 (2H, multiplet), 2.17 (1H, doublet of doublets, J = 11.6 and 24.0 Hz ), 2.09 (3H, singlet), 1.93 (3H, singlet), 1.29 (3H, singlet), 0.97 (3H, triplet, J = 7.4 Hz), 0.82 (3H doublet, J = 6.4 Hz), 0.75 (3H, doublet, J = 6.4 Hz).

Example 109
13- {2- [4- (N-Acetylglycyl) aminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCOCH ₂ NHAc, n = 0 (compound N 91)]
Mass spectrum (FAB-MS) m / z: 832 (M + H ⁺ , M = C ₄₆ H ₆₁ N ₃ O ₁₁ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.34 (1H, broad singlet), 7.46 (2H, doublet, J = 8.4 Hz), 7.26 (2H, doublet, J = 8 4 Hz), 6.48 (1H, broad singlet), 4.87 (1H, doublet, J = 10.5 Hz), 4.72 and 4.70 (2H, AB quartet, J = 14.4 Hz), 4.66 (1H, singlet), 4.09 (2H, doublet, J = 4.4 Hz), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 3.04 ( 1H, doublet of triplets, J = 2.1 and 8.9 Hz), 2.10 (3H, singlet), 1.93 (3H, singlet), 1.57 (3H, singlet), 1.54 (3H, singlet), 1.30 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.84-0.76 (6H, multiplet).

Example 110
13- [1- (4-Acetoxyacetylaminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHCOCH ₂ OAc , n = 0 (compound N 214)]
47.2 mg (0.40 mmol) of 3-acetoxyacetic acid, 0.028 ml (0.20 mmol) of triethylamine and 51.1 mg (0.20 mmol) of 2-chloro-1-methyl-pyridinium iodide were added to solution 87, 3 mg (0.10 mmol) 13- [2- (4-amino-phenyl) -2-methylpropionyloxy] -5-tert-butyldimethylsilyloxyiminomylbemycin A ₄ [prepared as described in Example 57 (a) - (d)] in 2.0 ml of methylene chloride and stirred for 1.5 hours. After this time, the reaction mixture was diluted with 20 ml of ethyl acetate and washed successively with 0.2 M aqueous citric acid solution, water, 4% (w / v) aqueous sodium bicarbonate and again with water. Then it was dried over anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure. The resulting residue was dissolved in 2.0 ml of methanol and 0.2 ml of a 1 M aqueous solution of hydrochloric acid was added. The reaction mixture was stirred at room temperature for 20 minutes, after which it was diluted with 20 ml of ethyl acetate and washed successively with water, 4% (w / v) aqueous sodium bicarbonate and again with water. After that, it was dried over anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure. The resulting residue was purified by silica gel column chromatography using a mixture of ethanol and methylene chloride with a volume ratio of 3: 97 as eluent, which provided 66.4 mg (yield 77.4%) of the title compound as an amorphous solid.

Mass spectrum (FAB-MS) m / z: 859 (M + H ⁺ , M = C ₄₈ H ₆₂ N ₂ O ₁₂ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.00 (1H, singlet), 7.74 (1H, singlet), 7.46 (2H, doublet, J = 8.6 Hz), 7.31 (2H, doublet, J = 8.6 Hz), 4.81 (1H, doublet, J = 10.4 Hz), 4.74 and 4.68 (2H, doublet of AB quartets, J = 1.9 and 14.6 Hz), 4.69 (2H, singlet), 4.65 (1H, singlet), 3.97 (1H, singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet) , 3.03 (1H, doublet of triplets, J = 2.2 & 9.3 Hz), 2.62 (2H, multiplet), 2.25 (3H, singlet), 1.93 (3H, singlet), 1 , 29 (3H, singlet), 0.97 (3H, triplet, J = 7.4 Hz), 0.82 (3H, doublet, J = 6.4 Hz), 0.77 (3H, doublet, J = 6.4 Hz).

Examples 111-113
The compounds of Examples 111-113 were prepared in accordance with the procedures described in Example 110.

Example 111
13- [1- (4- Ethoxyacetylaminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHCOCH ₂ OEt , n = 0 (compound N 213)]
Mass spectrum (FAB-MS) m / z: 845 (M + H ⁺ , M = C ₄₈ H ₆₄ N ₂ O ₁₁ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.27 (1H, singlet), 8.13 (1H, singlet), 7.49 (2H, doublet, J = 8.4 Hz), 7.30 (2H, doublet, J = 8.4 Hz), 4.81 (1H, doublet, J = 10.4 Hz), 4.74 and 4.67 (2H, doublet of AB quartets, J = 1.8 and 14.6 Hz), 4.65 (1H, singlet), 4.05 (2H, singlet), 3.97 (1H, singlet), 3.66 (2H, quartet, J = 7.2 Hz), 3 , 54 (1H, multiplet), 3.36 (1H, multiplet), 3.02 (1H, triplet doublet, J = 2.1 and 9.4 Hz), 2.61 (2H, multiplet), 1.93 (3H, singlet), 1.31 (3H, trip-years, J = 7.2 Hz), 1.29 (3H, singlet), 0.97 (3H, triplet, J = 7.4 Hz), 0 82 (3H, doublet, J = 6.4 Hz); 0.76 (3H, doublet, J = 6.4 Hz).

Example 112
13- [1- (4-Phenylthioacetylaminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHCOCH ₂ SPh , n = 0 (compound N 218)]
Mass spectrum (FAB-MS) m / z: 909 (M + H ⁺ , M = C ₅₂ H ₆₄ N ₂ O ₁₀ S).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.54 (1H, singlet), 8.09 (1H, singlet), 7.40 - 7.21 (9H, multiplet), 4.80 (1H, doublet, J = 10.4 Hz), 4.75 and 4.68 (2H, doublet of AB quartets, J = 1.8 and 14.6 Hz), 4.66 (1H, singlet), 3.97 ( 1H, singlet), 3.77 (2H, singlet), 3.54 (1H, multiplet), 3.36 (1H, multiplet), 3.02 (1H, doublet of triplets, J = 2.2 and 9.3 Hz), 2.60 (2H, multiplet), 1.93 (3H, doublet, J = 1.4 Hz), 1.29 (3H, singlet), 0.97 (3H, triplet, J = 7.2 Hz), 0.82 (3H, doublet, J = 6.5 Hz), 0.76 (3H, doublet, J = 6.4 Hz).

Example 113
13- [1- (4-Benzenesulfonylacetylaminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHCOCH ₂ SO ₂ Ph, n = 0 (compound N 217)]
Mass spectrum (FAB-MS) m / z: 941 (M + H ⁺ , M = C ₅₂ H ₆₄ N ₂ O ₁₂ S).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.46 (1H, singlet), 8.06 (1H, singlet), 7.92 (2H, doublet, J = 7.3 Hz), 7.70 (1H, doublet of doublets, J = 7.4 and 7.4 Hz), 7.58 (2H, doublet of doublets, J = 7.3 and 7.4 Hz), 7.42 (2H, doublet, J = 8 , 7 Hz), 7.31 (2H, doublet, J = 8.7 Hz), 4.82 (1H, doublet, J = 10.5 Hz), 4.75 and 4.68 (2H, doublet AB- quartets, J = 1.8 and 14.5 Hz), 4.65 (1H, singlet), 4.15 (2H, singlet), 3.97 (1H, singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 3.02 (1H, triplet doublet, J = 2.2 and 9.4 Hz), 2.62 (2H, multiplet), 1.93 (3H, doublet, J = 1 6 Hz), 1.31 (3H, singlet), 0.97 (3H, triplet, J = 7.3 Hz), 0.82 (3H, doublet, J = 6.5 Hz), 0.76 ( 3H, doublet, J = 6.5 Hz).

Example 114
13- {2- [4- (N-Methylcarbamoylamino) phenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCONHMe, n = 0 (compound N 132)]
11.4 mg (0.20 mmol) of methyl isocyanate was added to a solution of 101 mg (0.12 mmol) of 13- [2- (4-aminophenyl) -2-methylpropionyloxy] -5-tert-butyldimethylsilyloxyiminomylbemycin A ₄ [prepared as described in example 18 (a) and (b)] in 2.0 ml of methylene chloride and stirred at room temperature for 5 hours. After this time, the solvent was evaporated from the reaction mixture under reduced pressure. The resulting residue was dissolved in 2.0 ml of methanol, and 0.2 ml of a 1 M aqueous solution of hydrochloric acid was added to the resulting solution. The reaction mixture was stirred at room temperature for 20 minutes, after which it was diluted with 20 ml of ethyl acetate and washed successively with water, 4% (w / v) aqueous sodium bicarbonate and again with water. Then it was dried over anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure. The resulting residue was purified by silica gel column chromatography using a mixture of ethyl acetate and hexane with a volume ratio of 6: 4 as eluent, which provided 87 mg (yield 91%) of the title compound as an amorphous solid.

Mass spectrum (FAB-MS) m / z: 790 (M + H ⁺ , M = C ₄₄ H ₅₉ N ₃ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.14 (1H, broad singlet), 7.26 (2H, doublet, J = 8.6 Hz), 7.20 (2H, doublet, J = 8 6 Hz), 6.27 (1H, broad singlet), 4.87 (1H, doublet, J = 10.6 Hz), 4.72 and 4.69 (2H, AB quartet, J = 15.2 Hz), 4.66 (1H, singlet), 3.95 (1H, singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 2, 84 (3H, doublet, J = 4.7 Hz), 1.93 (3H, singlet), 1.58 (3H, singlet), 1.54 (3H, singlet), 1.31 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz); 0.83-0.81 (6H, multiplet).

Examples 115-119
The compounds of examples 115-119 were obtained in accordance with the procedures described in example 114.

Example 115
13- {2- [4- (N-phenylcarbamoylamino) phenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCONHPh, n = 0 (compound N 144)]
Mass spectrum (FAB-MS) m / z: 852 (M + H ⁺ , M = C ₄₉ H ₆₁ N ₃ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.22 (1H, broad singlet), 6.69 (1H, broad singlet), 6.64 (1H, broad singlet), 4.87 (1H, doublet , J = 10.6 Hz), 4.72 and 4.70 (2H, AB quartet, J = 14.5 Hz), 4.66 (1H, singlet), 3.95 (1H, singlet), 3 55 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 1.92 (3H, singlet), 1.58 (3H, singlet), 1.54 (3H, singlet), 1.32 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (6H, doublet, J = 6.6 Hz).

Example 116
13- {2- [4- (N-Methylthiocarbamoylamino) phenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCSNHMe, n = 0 (compound N 145)]
Mass spectrum (FAB-MS) m / z: 806 (M + H ⁺ , M = C ₄₄ H ₅₉ N ₃ O ₉ S).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.94 (1H, broad singlet), 7.61 (1H, broad singlet), 7.37 (2H, doublet, J = 8.6 Hz), 7 14 (2H, doublet, J = 8.6 Hz), 5.97 (1H, broad singlet), 4.89 (1H, doublet, J = 10.6 Hz), 4.72 and 4.70 (2H , AB- quartet, J = 14.5 Hz), 4.66 (1H, singlet), 3.96 (1H, singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 3 14 (3H, doublet, J = 4.6 Hz), 3.03 (1H, doublet of doublets, J = 2.0 and 9.2 Hz), 1.93 (3H, singlet), 1.59 (3H singlet), 1.57 (3H, singlet), 1.34 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (6H, doublet, J = 6, 5 Hz).

Example 117
13- {1- [4- (N-Methylcarbamoylamino) phenyl] cyclobutanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₃ , R ³ = 4-NHCONHMe, n = 0 (compound N 494)]
Mass spectrum (FAB-MS) m / z: 802 (M + H ⁺ , M = C ₄₅ H ₅₉ N ₃ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.30 (1H, broad singlet), 7.22 (4H, singlet), 6.31 (1H, broad singlet), 4.85 (1H, doublet, J = 10.6 Hz), 4.73 and 4.70 (2H, AB-quartet, J = 14.5 Hz), 4.66 (1H, singlet), 3.95 (1H, singlet), 3, 55 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, doublet of doublets, J = 2.3 & 9.2 Hz), 2.84 (3H, doublet, J = 4.6 Hz), 2.53-2.42 (3H, multiplet), 1.93 (3H, singlet), 1.35 (3H, singlet), 0.97 (3H, triplet, J = 7.3 Hz), 0.82 (3H, doublet, J = 6.6 Hz); 0.77 (3H, doublet, J = 6.3 Hz).

Example 118
13- {1- [4- (N-Phenylcarbamoylamino) phenyl] cyclobutanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₃ , R ³ = 4-NHCONHPh, n = 0 (compound N 500)]
Mass spectrum (FAB-MS) m / z: 864 (M + H ⁺ , M = C ₅₀ H ₆₁ N ₃ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.56 (1H, singlet), 7.35-7.30 (4H, multiplet), 7.25-7.19 (4H, multiplet), 7, 15-7.10 (1H, multiplet), 6.89 (1H, singlet), 6.75 (1H, singlet), 4.86 (1H, doublet, J = 10.4 Hz), 4.75 and 4 68 (2H, doublet of AB quartets, J = 1.6 and 14.8 Hz), 4.67 (1H, singlet), 3.95 (1H, singlet), 3.55 (1H, multiplet), 3 36 (1H, multiplet), 3.04 (1H, multiplet), 2.84 - 2.72 (2H, multiplet), 1.91 (3H, singlet), 1.36 (3H, singlet), 0, 96 (3H, triplet, J = 7.4 Hz), 0.82 (3H, doublet, J = 6.5 Hz), 0.79 (3H, doublet, J = 6.5 Hz).

Example 119
13- {1- [4- (N-Phenylcarbamoylamino) phenyl] cyclopentanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHCONHPh, n = 0 (compound N 309)]
Mass spectrum (FAB-MS) m / z: 878 (M + H ⁺ , M = C ₅₁ H ₆₃ N ₃ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.80 (1H, broad singlet), 7.40-7.00 (1H, multiplet), 4.86 (1H, doublet, J = 10.3 Hz ), 4.74-4.66 (2H, AB quartet, J = 15.5 Hz), 4.66 (1H, singlet), 3.95 (1H, singlet), 3.53 (1H, multiplet) , 3.36 (1H, multiplet), 3.01 (1H, multiplet), 2.60 (2H, multiplet), 1.88 (3H, singlet), 1.34 (3H, singlet), 0.95 ( 3H, triplet, J = 7.2 Hz), 0.81 (3H, doublet, J = 6.3 Hz), 0.76 (3H, doublet, J = 6.4 Hz).

Example 120
13- {1- [4- (N-Methylcarbamoylamino) phenyl] cyclopropanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₂ , R ³ = 4-NHCONHMe, n = 0 (compound N 432)]
120 (a) 13- {1- [4- (1,2,4-triazolo [4,3-a] pyridin-3-one-2-carbonyl) aminophenyl] cyclopropanecarbonyloxy} -5-tert-butyldimethylsilyloxyiminomylbemycin A ₄
13- [1- (4-Nitrophenyl) -cyclopropanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ [prepared as described in Example 6] was converted to 13- [1- (4-aminophenyl) cyclopropanecarbonyloxy] -5-tert-butyldimethylsilyloxyiminomylbemycin A ₄ in accordance with the procedures presented in example 18 (a) and (b).

845 mg (1.0 mmol) of this amino derivative were dissolved in 10 ml methylene chloride and at a temperature of 4 ^o C was added 0.081 (1.0 mmol) of pyridine and 198 mg (1.0 mmol) with chloroform-2-1,2,4-triazolo [4,3-a] - pyridin-3-one. The reaction mixture was stirred at room temperature for 20 minutes, after which it was diluted with 100 ml of ethyl acetate and washed successively with 0.2 M aqueous citric acid solution, water, 4% (w / v) aqueous sodium bicarbonate and again with water. Then it was dried over anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure. The resulting residue was purified by silica gel column chromatography using a mixture of ethyl acetate and hexane with a volume ratio of 1: 1 as eluent, which afforded 995 mg (97.4% yield) of the title compound as an amorphous solid.

120 (b) 13- {1- [4- (N- Metilkarbamoilamino) phenyl] tsiklopropan- carbonyloxy} -5-hydroxyimino-A ₄
153 mg (0.15 mmol) 13- {1- [4- (1,2,4-triazolo [4,3-a] pyridin-3-one-2-carbonyl) aminophenyl] cyclopropanecarbonyloxy} -5-tert- butyldimethylsilyloxyiminomylbemycin A ₄ [prepared as described in (a) above] was dissolved in 1.0 ml of N-methylpyrrolidone. To the resulting solution was added 19.4 mg (0.25 mmol) of a 40% (v / v) solution of methylamine in water and stirred at room temperature for 1 hour. The reaction mixture was diluted with 20 ml of ethyl acetate and washed successively with water, 0.2 M aqueous citric acid, water, 4% (w / v) aqueous sodium bicarbonate and again with water. Then it was dried over anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure. The resulting residue was dissolved in 2.0 ml of methanol and 0.2 ml of a 1 M aqueous solution of hydrochloric acid was added. The reaction mixture was stirred at room temperature for 20 minutes, after which it was diluted with 20 ml of ethyl acetate and washed successively with water, 4% (w / v) aqueous sodium bicarbonate and again with water. After that, it was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by chromatography on silica gel columns using a mixture of ethanol and methanol with a volume ratio of 5: 95 as eluent, which allowed to obtain 109 mg (yield 92.4%) of the title compound as an amorphous solid.

Mass spectrum (FAB-MS) m / z: 788 (M + H ⁺ , M = C ₄₄ H ₅₇ N ₃ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.86 (1H, singlet), 7.27 (2H, doublet, J = 8.4 Hz), 7.21 (2H, doublet, J = 8, 4 Hz), 6.53 (1H, singlet), 4.87 (1H, doublet, J = 10.4 Hz), 4.81 (1H, multiplet), 4.73 and 4.67 (2H, doublet AB quartets, J = 1.8 and 14.6 Hz), 4.67 (1H, singlet), 3.93 (1H, singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet) , 3.03 (1H, doublet of doublets, J = 2.1 & 9.4 Hz), 2.83 (3H, doublet, J = 4.9 Hz), 1.93 (3H, singlet), 1.38 (3H, singlet), 1.16 (2H, multiplet), 0.97 (3H, triplet, J = 7.3 Hz), 0.92 (3H, doublet, J = 6.5 Hz), 0.82 (3H, doublet, J = 6.5 Hz).

Examples 121-124
The compounds of Examples 121-124 were prepared in accordance with the procedures described in Example 120.

Example 121
13- {1- [4- (1-Pyrrolidinylcarbonylamino) phenyl] cyclopropanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, 2 => C (CH ₂ ) ₂ , R ³ = 4-NHCO (1-pyrrolidinyl), n = 0 (compound N 437)]
Mass spectrum (FAB-MS) m / z: 828 (M + H ⁺ , M = C ₄₇ H ₆₁ N ₃ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.37 (1H, singlet), 7.35 (2H, doublet, J = 8.6 Hz), 7.23 (2H, doublet, J = 8, 6 Hz), 6.15 (1H, singlet), 4.86 (1H, doublet, J = 10.4 Hz), 4.73 and 4.67 (2H, AB quartet doublet, J = 1.9 and 14.7 Hz), 4.66 (1H, singlet), 3.92 (1H, singlet), 3.55 (1H, multiplet), 3.47 (4H, multiplet), 3.36 (1H, multiplet) , 3.03 (1H, doublet of doublets, J = 2.2 & 9.4 Hz), 1.98 (4H, multiplet), 1.93 (3H, doublet, J = 1.5 Hz), 1.36 (3H, singlet), 1.15 (2H, multiplet), 0.97 (3H, triplet, J = 7.3 Hz), 0.90 (3H, doublet, J = 6.5 Hz), 0.83 (3H, doublet, J = 6.5 Hz).

Example 122
13- {1- [4- (N-Butylcarbamoylamino) phenyl] cyclopropanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4 -NHCONHBu, n = 0 (compound N 138)]
Mass spectrum (FAB-MS) m / z: 832 (M + H ⁺ , M = C ₄₇ H ₆₅ N ₃ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.24 (1H, broad singlet), 7.25 (2H, doublet, J = 8.6 Hz), 7.20 (2H, doublet, J = 8 6 Hz), 6.28 (1H, broad singlet), 4.87 (1H, doublet, J = 10.6 Hz), 4.72 and 4.69 (2H, AB quartet, J = 14.5 Hz), 4.66 (1H, singlet), 3.95 (1H, singlet), 3.56 (1H, multiplet), 3.36 (1H, multiplet), 3.25 (2H, quartet, J = 6 , 6 Hz), 3.03 (1H, multiplet), 1.93 (3H, singlet), 1.57 (3H, singlet), 1.54 (3H, singlet), 1.31 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz); 0.84-0.81 (6H, multiplet).

Example 123
13- {1- [4-N-tert-Butylcarbamoylamino) phenyl] cyclopropanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCONHtBu, n = 0 (compound N 139)]
Mass spectrum (FAB-MS) m / z: 832 (M + H ⁺ , M = C ₄₇ H ₆₅ N ₃ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ / ppm: 8.22 (1H, broad singlet), 7.23 (2H, doublet, J = 8.6 Hz), 7.17 (2H, doublet, J = 8.6 Hz), 6.13 (1H, broad singlet), 4.87 (1H, doublet, J = 10.6 Hz), 4.72 and 4.69 (2H, AB quartet, J = 14, 5 Hz), 4.66 (1H, singlet), 3.95 (1H, singlet), 3.56 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, triplet doublet, J = 1.7 and 8.9 Hz), 1.93 (3H, singlet), 1.56 (3H, singlet), 1.53 (3H, singlet), 1.37 (9H, singlet), 1.32 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.84-0.80 (6H, multiplet).

Example 124
13- {1- [4- (N-Cyclohexylcarbamoylamino) phenyl] cyclopropanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4 -NHCONH-cHx, n = 0 (compound N 140)]
Mass spectrum (FAB-MS) m / z: 858 (M + H ⁺ , M = C ₄₉ H ₆₇ N ₃ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.17 (1H, broad singlet), 7.25 (2H, doublet, J = 8.6 Hz), 7.19 (2H, doublet, J = 8 6 Hz), 6.18 (1H, broad singlet), 4.87 (1H, doublet, J = 10.5 Hz), 4.72 and 4.69 (2H, AB quartet, J = 14.5 Hz), 4.66 (1H, singlet), 3.95 (1H, singlet), 3.56 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, triplet doublet, J = 1.9 and 9.2 Hz), 1.93 (3H, singlet), 1.57 (3H, singlet), 1.54 (3H, singlet), 1.31 (3H, singlet), 0.98 ( 3H, triplet, J = 7.3 Hz), 0.84-0.81 (6H, multiplet).

Example 125
13- {1- [4- (Pyrimidin-2-ylthioacetylamino) phenyl] cyclopropanecarbonyloxy} - 5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, 2 => C (CH ₂ ) ₂ , R ³ = 4-NHCOCH ₂ S- (2-pyrimidyl), n = 0 (compound N 406)]
13- [1 - (4-Nitrophenyl) cyclopropanecarbonyloxy] -5-hadroxyiminomylbemycin A ₄ (prepared as described in Example 6) was converted to 13- [1- (4-bromoacetylaminophenyl) cyclopropanecarbonyloxy] -5-tert-butyldimethylsilyloxyimin ₄ in accordance with the procedures presented in example 18.

 115 mg (0.12 mmol) of this bromoacetyl derivative was dissolved in 2.0 ml of N-methylpyrrolidone and 22.4 mg (0.20 mmol) of 2-mercaptopirimidine and 6.5 mg (0.15 mmol) of sodium hydride were added [in 55% (in terms of weight to volume) suspension in mineral oil]. The reaction mixture was stirred at room temperature for 30 minutes, after which it was diluted with 20 ml of ethyl acetate and washed successively with 0.2 M aqueous citric acid, water, 4% (w / v) aqueous sodium bicarbonate and again with water. Then it was dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was dissolved in 2.0 ml of methanol and 0.2 ml of a 1 M aqueous solution of hydrochloric acid was added. The reaction mixture was stirred at room temperature for 20 minutes, diluted with 20 ml of ethyl acetate and washed successively with water, 4% (w / v) aqueous sodium bicarbonate and again with water. After that, it was dried over anhydrous sodium sulfate, and the solvent was removed by evaporation under reduced pressure. The obtained residue was purified by silica gel column chromatography using a mixture of ethanol and methylene chloride with a volume ratio of 2.5: 97.5 as eluent, which allowed to obtain 105 mg (yield 99.1%) of the title compound as an amorphous solid .

Mass spectrum (FAB-MS) m / z: 883 (M + H ⁺ M = C ₄₈ H ₅₈ N ₄ O ₁₀ S).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 9.13 (1H, singlet), 8.63 (2H, doublet, J = 5.1 Hz), 8.28 (1H, singlet), 7.40 (2H, doublet, J = 8.4 Hz), 7.25 (2H, doublet, J = 8.4 Hz), 7.13 (1H, triplet, J = 5.1 Hz), 4.85 (1H doublet, J = 10.5 Hz), 4.73 and 4.66 (2H, doublet of AB quartets, J = 2.0 and 14.5 Hz), 4.65 (1H, singlet), 3.93 (3H, singlet), 3.54 (1H, multiplet), 3.36 (1H, multiplet), 3.02 (1H, doublet of doublets, J = 2.2 & 9.4 Hz), 1.93 (3H doublet, J = 1.5 Hz), 1.36 (3H, singlet), 1.13 (2H, multiplet), 0.97 (3H, triplet, J = 7.3 Hz), 0.89 (3H doublet, J = 6.5 Hz), 0.82 (3H, doublet, J = 6.5 Hz).

Examples 126-127
The compounds of Examples 126-127 were prepared in accordance with the procedures described in Example 125.

Example 126
13- {1- [4- (Thiazolidin-2-ylthioacetylamino) phenyl] cyclopropanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₂ , R ³ = 4-NHCOCH ₂ S- (2-thiazolidinyl), n = 0 (compound N 408)]
Mass spectrum (FAB-MS) m / z: 890 (M + H ⁺ , M = C ₄₇ H ₅₉ N ₃ O ₁₀ S ₂ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.21 (1H, singlet), 7.41 (2H, doublet, J = 8.5 Hz), 7.27 (2H, doublet, J = 8, 5 Hz), 4.87 (1H, doublet, J = 10.5 Hz), 4.73 and 4.66 (2H, doublet of AB quartets, J = 2.0 and 14.5 Hz), 4.65 (1H, singlet), 4.31 (2H, triplet, J = 8.0 Hz), 3.92 (3H, singlet), 3.79 (2H, singlet), 3.56 (1H, multiplet), 3 54 (2H, triplet, J = 8.0 Hz), 3.36 (1H, multiplet), 3.03 (1H, doublet of doublets, J = 2.2 and 9.4 Hz), 1.93 (3H doublet, J = 1.4Hz), 1.37 (3H, singlet), 1.14 (2H, multiplet), 0.97 (3H, triplet, J = 7.3 Hz), 0.91 (3H, doublet, J = 6.5 Hz), 0.82 (3H, doublet, J = 6.5 Hz).

Example 127
13- {1- [4- (Pyridin-2-ylthioacetylamino) phenyl] cyclopropanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₂ , R ³ = 4-NHCOCH ₂ S- (1-pyridyl), n = 0 (compound N 407)]
Mass spectrum (FAB-MS) m / z: 882 (M + H ⁺ , M = C ₄₉ H ₅₉ N ₃ O ₁₀ S).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.55 (1H, doublet, J = 5.2 Hz), 8.18 (1H, singlet), 7.60 (1H, multiplet), 7.42 (2H, doublet, J = 8.6 Hz), 7.32 (1H, doublet, J = 8.0 Hz), 7.25 (2H, doublet, J = 8.6 Hz), 7.16 (1H doublet of doublets, J = 5.2 and 7.2 Hz), 4.85 (1H, doublet, J = 10.5 Hz), 4.73 and 4.66 (2H, doublet of AB quartets, J = 2 0 and 14.6 Hz), 4.65 (1H, singlet), 3.92 (1H, singlet), 3.89 (2H, singlet), 3.54 (1H, multiplet), 3.36 (1H multiplet), 3.03 (1H, doublet of doublets, J = 2.2 & 9.4 Hz), 1.93 (3H, multiplet), 1.36 (3H, singlet), 1.13 (2H, multiplet ), 0.97 (3H, triplet, J = 7.3 Hz), 0.89 (3H, doublet, J = 6.4 Hz), 0.82 (3H, doublet, J = 6.5 Hz).

Examples 128-137
The compounds of Examples 128-137 were prepared in accordance with the procedures described in Example 1.

Example 128
3- {1- [4- (N-Methylacetylamino) phenyl] cyclopentanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-N (Me) Ac, n = 0 (compound N 193)]
Mass spectrum (FAB-MS) m / z: 815 (M + H ⁺ , M = C ₄₇ H ₆₂ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.70 (1H, broad singlet), 7.38 (2H, doublet, J = 8.3 Hz), 7.11 (2H, doublet, J = 8 , 3 Hz), 4.81 (1H, doublet, J = 10.5 Hz), 4.74 and 4.66 (2H, AB quartet, J = 14.9 Hz), 4.65 (1H, singlet ), 3.95 (1H, broad singlet), 3.55 (1H, multiplet), 3.35 (1H, multiplet), 3.23 (3H, singlet), 3.02 (1H, multiplet), 2, 65 (2H, multiplet), 1.92 (3H, singlet), 1.84 (3H, singlet), 1.30 (3H, singlet), 0.97 (3H, triplet, J = 7.2 Hz), 0.82 (3H, doublet, J = 6.3 Hz); 0.76 (3H, doublet, J = 6.5 Hz).

Example 129
13- {1- [4- (N-Butylacetylamino) phenyl] cyclopentanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-N (Bu) Ac, n = 0 (compound N 196)]
Mass spectrum (FAB-MS) m / z: 857 (M + H ⁺ , M = C ₅₀ H ₆₈ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.11 (1H, singlet), 7.38 (2H, doublet, J = 8.6 Hz), 7.07 (2H, doublet, J = 8, 6 Hz), 4.80 (1H, doublet,; = 10.4 Hz), 4.74 and 4.67 (2H, AB quartet, J = 14.4 Hz), 4.65 (1H, singlet) 3.97 (1H, singlet), 3.66 (2H, triplet, J = 7.6 Hz), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, multiplet), 2.65 (2H, multiplet), 1.93 (3H, singlet), 1.78 (3H, singlet), 1.28 (3H, singlet), 0.97 (3H, triplet, J = 7 , 3 Hz), 0.87 (3H, triplet, J = 7.2 Hz), 0.82 (3H, doublet, J = 6.4 Hz), 0.72 (3H, doublet, J = 6.4 Hz).

Example 130
13- {1- [4- (N-Methylmethanesulfonylamino) phenyl] cyclopentanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-N (Me) SO ₂ Me, n = 0 (compound N 316)]
Mass spectrum (FAB-MS) m / z: 851 (M + H ⁺ , M = C ₄₆ H ₆₂ N ₂ O ₁₁ S).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.13 (1H, singlet), 7.35 (2H, doublet, J = 8.7 Hz), 7.29 (2H, doublet, J = 8, 7 Hz), 4.80 (1H, doublet, J = 10.4 Hz), 4.74 and 4.67 (2H, doublet of AB quartets, J = 1.8 and 14.2 Hz), 4.65 (1H, singlet), 3.97 (1H, singlet), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 3.29 (3H, singlet), 3.02 (1H, multiplet) 2.80 (3H, singlet), 2.62 (2H, multiplet), 1.93 (3H, singlet), 1.27 (3H, singlet), 0.97 (3H, triplet, J = 7.2 Hz), 0.82 (3H, doublet, J = 6.4 Hz), 0.75 (3H, doublet, J = 6.4 Hz).

Example 131
13- {1- [4- (N-Butylmethanesulfonylamino) phenyl] cyclopentanecarbonyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-N (Bu) SO ₂ Me, n = 0 (compound N 319)]
Mass spectrum (FAB-MS) m / z: 893 (M + H ⁺ , M = C ₄₉ H ₆₈ N ₂ O ₁₁ S).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.03 (1H, singlet), 7.36 (2H, doublet, J = 8.7 Hz), 7.25 (2H, doublet, J = 8, 7 Hz), 4.79 (1H, doublet, J = 10.7 Hz), 4.74 and 4.67 (2H, doublet of AB quartets, J = 1.8 and 14.6 Hz), 4.65 (1H, singlet), 3.97 (1H, singlet), 3.64 (2H, triplet, J = 6.8 Hz), 3.55 (1H, multiplet), 3.36 (1H, multiplet), 3 03 (1H, multiplet), 2.83 (3H, singlet), 2.65 (2H, multiplet), 1.93 (3H, singlet), 1.27 (3H, singlet), 0.97 (3H, triplet, J = 7.3 Hz), 0.86 (3H, triplet, J = 7.2 Hz), 0.82 (3H, doublet, J = 6.4 Hz), 0.72 (3H, doublet, J = 6.4 Hz).

Example 132
13- {2- [4- (2-Oxopiperidino) phenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4- (2-oxo-1-piperidyl), n = 0 (compound N 161)]
Mass spectrum (FAB-MS) m / z: 815 (M + H ⁺ , M = C ₄₇ H ₆₂ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.18 (1H, singlet), 7.31 (2H, doublet, J = 8.5 Hz), 7.18 (2H, doublet, J = 8, 5 Hz), 4.87 (1H, doublet, J = 10.8 Hz), 4.73 and 4.66 (2H, doublet of AB quartets, J = 1.8 and 14.6 Hz), 4.65 (1H, singlet), 3.96 (1H, broad singlet), 3.62 - 3.52 (3H, multiplet), 3.36 (1H, multiplet), 3.03 (1H, multiplet), 2.57 (2H, multiplet), 1.92 (3H, singlet), 1.58 (3H, singlet), 1.55 (3H, singlet), 1.29 (3H, singlet), 0.98 (3H, triplet, J = 7.4 Hz), 0.84-0.82 (6H, multiplet).

Example 133 13- {2- [4- (2-Oxo-1-pyrrolidinyl) phenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4- (2-oxo-1-pyrrolidinyl), n = 0 (compound N 163)]
Mass spectrum (FAB-MS) m / z: 801 (M + H ⁺ , M = C ₄₆ H ₆₀ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.80 (1H, broad singlet), 7.55 (2H, doublet, J = 8.6 Hz), 7.30 (2H, doublet, J = 8 , 6 Hz), 4.88 (1H, doublet, J = 10.6 Hz), 4.74 and 4.65 (2H, AB quartet, J = 14.4 Hz), 4.65 (1H, singlet ), 3.96 (1H, singlet), 3.71 (2H, singlet), 3.57 (1H, multiplet), 3.38 (1H, multiplet), 3.04 (1H, multiplet), 2.62 (2H, triplet, J = 8.2 Hz), 2.17 (2H, triplet, J = 7.5 Hz), 1.93 (3H, singlet), 1.57 (3H, singlet), 1.54 (3H, singlet), 1.32 (3H, singlet), 0.98 (3H, triplet, J = 7.2 Hz), 0.85-0.82 (6H, multiplet).

Example 134
13- {2- [4- (2-Oxoazetidin-1-yl) phenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me ) ₂ , R ³ = 4- (2-oxo-1-azetidinyl), n = 0 (compound N 160)]
Mass spectrum (FAB-MS) m / z: 787 (M + H ⁺ , M = C ₄₅ H ₅₈ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.99 (1H, singlet), 7.28-7.26 (4H, multiplet), 4.87 (1H, doublet, J = 10.8 Hz) 4.74-4.67 (2H, doublet of AB quartets, J = 2.0 and 14.4 Hz), 4.66 (1H, singlet), 3.97 (1H, singlet), 3.63- 3.60 (2H, multiplet), 3.57 (1H, multiplet), 3.38 (1H, multiplet), 3.13-3.10 (2H, multiplet), 3.03 (1H, multiplet), 1 93 (3H, singlet), 1.58 (3H, singlet), 1.54 (3H, singlet), 1.32 (3H, singlet), 0.98 (3H, triplet, J = 7.2 Hz) 0.84-0.81 (6H, multiplet).

Example 135
13- {2- [4- (2,6-dioxopiperidino) phenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4- (2,6-dioxo-1-piperidyl), n = 0 (compound N 162)]
Mass spectrum (FAB-MS) m / z: 829 (M + H ⁺ , M = C ₄₇ H ₆₀ N ₂ O ₁₁ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.12 (1H, singlet), 7.36 (2H, doublet, J = 8.6 Hz), 7.01 (2H, doublet, J = 8, 6 Hz), 4.86 (1H, doublet, J = 10.4 Hz), 4.72 and 4.66 (2H, doublet of AB quartets, J = 2.1 and 14.5 Hz), 4.65 (1H, singlet), 3.96 (1H, singlet), 3.56 (1H, multiplet), 3.35 (1H, multiplet), 3.04 (1H, multiplet), 2.81 (4H, triplet, J = 6.6 Hz), 2.11 (2H, multiplet), 1.93 (3H, singlet), 1.61 (3H, singlet), 1.56 (3H, singlet), 1.23 (3H, singlet), 0.98 (3H, triplet, J = 7.2 Hz), 0.84 (3H, doublet, J = 6.5 Hz), 0.83 (3H, doublet, J = 6.4 Hz) .

Example 136
13- {2- [4- (2,5-dioxo-1-pyrrolidinyl) phenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4- (2,5-dioxo-1-pyrrolidinyl), n = 0 (compound N 164)]
Mass spectrum (FAB-MS) m / z: 815 (M + H ⁺ , M = C ₄₆ NH ₅₈ N ₂ O ₁₁ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.25 (1H, singlet), 7.39 (2H, doublet, J = 8.5 Hz), 7.23 (2H, doublet, J = 8, 5 Hz), 4.88 (1H, doublet, J = 10.6 Hz), 4.73 and 4.67 (2H, doublet of AB quartets, J = 2.0 and 14.5 Hz), 4.65 (1H, singlet), 3.97 (1H, singlet), 3.56 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, doublet of doublets, J = 2.2 and 9, 5 Hz), 2.90 (4H, singlet), 1.93 (3H, doublet, J = 1.5 Hz), 1.60 (3H, singlet), 1.56 (3H, singlet), 1.27 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.84 (3H, doublet, J = 6.5 Hz), 0.83 (3H, doublet, J = 8, 5 Hz).

Example 137
13- {2- [4- (2-Oxooxazolin-3-yl) phenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me ) ₂ , R ³ = 4- (2-oxo-3-oxazoline), n = 0 (compound N 165)]
Mass spectrum (FAB-MS) m / z: 803 (M + H ⁺ , M = C ₄₅ H ₅₈ N ₂ O ₁₁ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.19 (1H, broad singlet), 7.48 (2H, doublet, J = 9.0 Hz), 7.30 (2H, doublet, J = 9 , 0 Hz), 4.88 (1H, doublet, J = 10.5 Hz), 4.74 and 4.66 (2H, doublet of AB quartets, J = 2.0 and 14.5 Hz), 4, 65 (1H, singlet), 4.49 (2H, multiplet), 4.05 (2H, multiplet), 3.97 (1H, singlet), 3.57 (1H, multiplet), 3.36 (1H, multiplet ), 3.04 (1H, doublet of doublets, J = 2.2 & 9.4 Hz), 1.93 (3H, doublet, J = 1.4 Hz), 1.58 (3H, singlet), 1, 55 (3H, singlet), 1.32 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.83 (3H, doublet, J = 6.5 Hz), 0, 82 (3H, doublet, J = 6.5 Hz).

Examples 138-139
The compounds of Examples 138-139 were prepared from 13- [2- (3-nitro-phenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ (prepared as described in Example 2) in accordance with the procedures presented in Example 18.

Example 138
13- [2- (3-Acetylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 3-NHAc , n = 0 (compound N 32)]
Mass spectrum (FAB-MS) m / z: 775 (M + H ⁺ , M = C ₄₄ H ₅₈ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.87 (1H, broad singlet), 7.50 (1H, doublet, J = 8.6 Hz), 7.39 (1H, singlet), 7, 22 (1H, doublet, J = 7.9 Hz), 7.10 (1H, broad singlet), 7.02 (1H, doublet, J = 7.9 Hz), 4.87 (1H, doublet, J = 10.6 Hz), 4.71 and 4.69 (2H, AB quartet, J = 13.9 Hz), 4.65 (1H, singlet), 3.95 (1H, singlet), 3.57 ( 1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 2.18 (3H, singlet), 1.93 (3H, singlet), 1.57 (3H, singlet), 1.54 (3H, singlet), 1.28 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.84-0.81 (6H, multiplet).

Example 139
13- [2- (3-Methanesulfonylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 3-NHSO ₂ Me, n = 0 (compound N 150)]
Mass spectrum (FAB-MS) m / z: 711 (M + H ⁺ , M = C ₄₃ H ₅₈ N ₂ O ₁₁ S).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 7.76 (1H, broad singlet), 7.50-7.10 (24, multiplet), 6.33 (1H, broad singlet), 4.88 ( 1H, doublet, J = 10.6 Hz), 4.71 and 4.70 (2H, AB-quartet, J = 14.5 Hz), 4.65 (1H, singlet), 3.94 (1H, singlet ), 3.57 (1H, multiplet), 3.36 (1H, multiplet), 3.04 (1H, multiplet), 2.99 (3H, singlet), 1.93 (3H, singlet), 1.58 (3H, singlet), 1.56 (3H, singlet), 1.31 (3H, singlet), 0.98 (3H, triplet, J = 7.3 Hz), 0.84-0.81 (6H, multiplet).

Example 140
13- [1- (4-Acetylaminophenyl) cyclopentanecarbonyloxy] - 5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (CH ₂ ) ₄ , R ³ = 4-NHAc, n = 0 (connection N 192)]
The title compound was obtained from 15-hydroxy-5-oxomylbemycin A ₃ in accordance with the method described in examples 57 and 59.

Mass spectrum (FAB-MS) m / z: 787 (M + H ⁺ , M = C ₄₅ H ₅₈ N ₂ O ₁₀ ).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.11 (1H, singlet), 7.41 (2H, doublet, J = 8.6 Hz), 7.28 (2H, doublet, J = 8, 6 Hz), 7.13 (1H, singlet), 4.81 (1H, doublet, J = 10.4 Hz), 4.75 and 4.69 (2H. AB quartet, J = 14.7 Hz) 4.65 (1H, singlet), 3.97 (1H, singlet), 3.52 (1H, multiplet), 3.36 (1H, multiplet), 3.21 (1H, multiplet), 2.61 ( 2H, multiplet), 2.17 (3H, singlet), 1.93 (3H, singlet), 1.29 (3H, singlet), 1.14 (3H, doublet, J = 6.4 Hz), 0, 83 (3H, doublet, J = 6.5 Hz), 0.75 (3H, doublet, J = 6.5 Hz).

Examples 141-142
The compounds of Examples 141-142 were prepared from 15-hydroxy-5-oxomylbemycin A ₄ in accordance with the procedures described in Examples 57 and 110.

Example 141
13- {2- [4- (1-Methoxycarbonylpyrrolidine-2-carbonylamino) phenyloxy]} - 5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = CO, Z => C (Me) ₂ , R ³ = 4-NHCO (1-COOMe-2-pyrrolidinyl), n = 0 (compound N 111)]
Mass spectrum (FAB-MS) m / z: 1053 (M + H ⁺ + triethanolamine = 903 + 1 + 149).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.63 (1H, broad singlet), 7.34 (2H, doublet, J = 8.8 Hz), 6.74 (2H, doublet, J = 8 , 8 Hz), 5.86 - 5.79 (3H, multiplet), 5.45-5.30 (3H, multiplet), 5.02 (1H, doublet, J = 10.9 Hz), 4.79 -4.68 (2H, AB quartet, J = 14.5 Hz), 4.67 (1H, singlet), 4.45 (1H, broad singlet), 4.00 (1H, singlet), 3.77 (3H, singlet), 3.73-3.38 (5H, multiplet), 3.65-3.42 (3H, multiplet), 3.37 (1H, multiplet), 3.06 (1H, multiplet).

Example 142
13- {2- [4- (N-Methoxycarbonylglycylamino) -2-methylpropionyloxyphenyloxy]} -5-hydroxyiminomylbemycin A ₄ [(I): R ¹ = ethyl, X = C = O, Z => C (Me) ₂ , R ³ = 4-NHCOCH ₂ NHCOOMe, n = 0 (compound N 80)]
Mass spectrum (FAB-MS) m / z: 1013 (M + H ⁺ + triethanolamine = 863 + 1 + 149).

Nuclear Magnetic Resonance Spectrum (CDCl ₃ ) δ ppm: 8.27 (1H, broad singlet), 7.83 (1H, broad singlet), 7.31 (2H, doublet, J = 8.9 Hz), 6 74 (2H, doublet, J = 8.9 Hz), 5.90-5.82 (3H, multiplet), 5.50-5.31 (4H, multiplet), 5.00 (1H, doublet, J = 10.4 Hz), 4.73-4.67 (2H, AB quartet, J = 14.4 Hz), 4.66 (1H, singlet), 3.98 (2H, singlet), 3.97 (1H, singlet), 3.74 (3H, singlet), 3.66 - 3.55 (1H, multiplet), 3.37 (1H, multiplet), 3.05 (1H, multiplet).

 Below is an example of a composition and additional activity data.

Capsules
Ingredient - mg / capsule
Comp. 16 - 20
Lactose - 100
Magnesium Stearate - 5
Total - 125
20 mg of crystals of the compound obtained in Example 16 of the present invention are placed in a suitable size gelatin capsule.

 Previously, the Applicant limited the claims to an insecticidal composition only. This was done at the time when the Applicant had data disclosing only the insecticidal activity of the compounds of this invention. The Applicant now has data showing the anthelmintic and acaricidal activity of the claimed compounds. The example of Test 1 clearly shows that the compounds of this invention have anthelmintic activity, and Example of Test 2 shows that the compounds also have potent acaricidal activity. The applicant asks to include the presented Examples and to clarify the composition as insecticidal, anthelmintic and acaricidal.

1. For anthelmintic activity
Test examples
Anthelmintic activity against Nippostrongylus brasiliensis, a nematode parasite for rats, is determined on groups of 3 wistar strain rats, the weight of which ranges from 40 to 60 g.

 Rats were injected subcutaneously with approximately 100 nematode larvae each. Solutions containing the test compound are orally administered 3 days after infection. Each solution was prepared by dissolving 1.0 mg of the test compound in 0.1 ml of dimethylformamide, and then 9.9 ml of polyethylene glycol (PEG 400) was added to the solution. From 0.4 to 0.6 ml of the indicated solution is orally given to each rat in accordance with its weight.

 Rats are killed 7 days after infection and the number of parasites is counted.

 The results are presented in table 3.

For acaricidal activity
Test examples
The action of milbemycin derivatives against nymphs Ornithodoros moubata of the third stage of development.

The effects of milbemycin derivatives are studied in vitro. Ticks are fed with cow serum, in which the compounds are dissolved in doses of 5, 10 and 20 ppm. The fed ticks are then placed in an incubator with a temperature of 26 ^° C. for 41 days until they are completely molted (see table 4).

Claims (24)

1. 13-Substituted derivatives of milbemycin of the formula I

in which R ¹ is a methyl group, an ethyl group, an isopropyl group or a sec-butyl group;
X is a carbonyl group or a methylene group;
Z is a group of formula (i) or (ii):
= C = (R ² ) ₂ (i)
= C = (CH ₂ ) _m (ii)
where R ² represents an alkyl group with 1-3 carbon atoms,
m is an integer from 2 to 5;
n is 0 or 1;
R ³ - nitro group, amino group, (C ₁ -C ₄ alkyl) amino group, di (C ₁ -C ₄ alkyl) amino group, alkoxy group with 1-4 carbon atoms, (C ₁ -C ₃ alkoxy) - (C ₂ - C ₃ alkoxyl) group, a group of the formula (iii), (iv), (v), (vi), (vii), (viii)

in which R ⁴ is an alkyl group with 1-6 carbon atoms, a substituted alkyl group with 1-6 carbon atoms, which is substituted by at least one of the following substituents α, a cycloalkyl group with 3-6 carbon atoms, an alkenyl group with 2- 6 carbon atoms, an alkynyl group with 2-6 carbon atoms, a carbocyclic aryl group with 6-14 carbon atoms in the ring, which may be unsubstituted or substituted by at least one of the following substituents γ, or a heterocyclic group with 3-6 atoms in the ring of which at least e one is a heteroatom of nitrogen and / or oxygen and / or sulfur, and this heterocyclic group may be unsubstituted or substituted by at least one of the following substituents γ;
R ⁵ is a hydrogen atom or an alkyl group with 1-4 carbon atoms;
R ⁶ is a hydrogen atom or an alkyl group with 1-6 carbon atoms;
R ⁷ is an alkyl group with 1-6 carbon atoms, a cycloalkyl group with 3-6 carbon atoms or a carbocyclic aryl group with 6-14 carbon atoms in the ring, which is not substituted;
Y is an oxygen atom or a sulfur atom;
r is 1, 2 or 3;
Q is a methylene group or a carbonyl group;
R ⁸ is an alkyl group with 1-4 carbon atoms;
R ⁹ is an alkyl group with 1-6 carbon atoms, a cycloalkyl group with 3-6 carbon atoms, a carbocyclic aryl group with 6-10 carbon atoms in the ring, which is not substituted;
substituents α are selected from the group consisting of halogen atoms, cyano groups, alkoxy groups with 1-4 carbon atoms, alkylthio groups with 1-4 carbon atoms, alkylsulfonyl groups with 1-4 carbon atoms, alkanoyloxy groups with 2-5 carbon atoms, alkoxycarbonyl groups with 2 -5 carbon atoms, carbocyclic aryloxy groups with 6-10 carbon atoms in the ring, carbocyclic arylthio groups with 6-10 carbon atoms in the ring, carbocyclic arylsulfonyl groups with 6-10 carbon atoms in the ring, amino groups, alkanoylamino groups with 2-5 atoms and carbon, alkoxycarbonylamino groups with 2-5 carbon atoms, carbocyclic arylcarbonylamino groups in which the aryl part has 6-10 carbon atoms in the ring, aralkylcarbonylamino groups in which the aryl part is carbocyclic and has 6-10 carbon atoms in the ring, and the alkyl part contains 1 -4 carbon atoms, carbocyclic aryl groups with 6-10 carbon atoms in the ring that may be unsubstituted or substituted by at least one of the substituents γ, of the group R ^h -S, where R ^h represents a heterocyclic group with 3-6 atoms in the ring, of which at least one is a heteroatom of nitrogen and / or oxygen and / or sulfur, the indicated heterocyclic group being optionally substituted, alkanoyl groups with 2-5 carbon atoms and an aralkyloxycarbonylamino group in which the aryl part is carbocyclic and has 6-10 carbon atoms in the ring, and the alkyl part contains 1-4 carbon atoms;
substituents γ are selected from the group consisting of halogen atoms, hydroxyl groups, cyano groups, nitro groups, alkyl groups with 1-4 carbon atoms, alkoxy groups with 1-4 carbon atoms and alkoxycarbonyl groups with 2-5 carbon atoms,
and their salts. 2. The compound according to claim 1, where R ¹ represents a methyl or ethyl group. 3. Compounds according to any one of the preceding paragraphs, where R ¹ represents an ethyl group. 4. Compounds according to any one of the preceding paragraphs, where Z represents a group of formula (i), and R ² represents a methyl or ethyl group. 5. Compounds according to any one of the preceding paragraphs, where Z represents a group of formula (i) and R ² is a methyl group.  6. Compounds according to any one of claims 1 to 3, where Z represents a group of formula (ii), and m means 2, 3 or 4.  7. Compounds according to any one of claims 1 to 3, where Z represents a group of formula (ii), a m means 2 or 4. 8. Compounds according to any one of the preceding paragraphs, where R ³ represents an amino group, a (C ₁ -C ₃ alkyl) amino group, a di (C ₁ -C ₃ alkyl) amino group, an alkoxy group with 1-3 carbon atoms or a group of formulas (iii) , (iv), (v), (vi) or (vii):

in which R ⁴ is an alkyl group with 1-4 carbon atoms, a substituted alkyl group with 1-3 carbon atoms, which is substituted by at least one of the substituents α ¹ listed below, a cycloalkyl group with 3-6 carbon atoms, an alkenyl group with 3 or 4 carbon atoms, an alkynyl group with 3 or 4 carbon atoms, a carbocyclic aryl group with 6-10 carbon atoms in the ring that may be unsubstituted or substituted by at least one of the substituents γ ¹ listed below, or a heterocyclic group with 3- 6 atoms in the ring, of which Raina least one heteroatom is nitrogen and / or oxygen and / or sulfur, said heterocyclic group may be unsubstituted or substituted by at least one of the following substituents γ ^1;
R ⁵ is a hydrogen atom or an alkyl group with 1-3 carbon atoms;
R ⁶ is a hydrogen atom or an alkyl group with 1-4 carbon atoms;
R ⁷ is an alkyl group with 1-6 carbon atoms or a carbocyclic aryl group with 6-10 carbon atoms in the ring, which is not substituted;
Y is an oxygen atom or a sulfur atom;
r is 1, 2 or 3;
Q is a methylene group or a carbonyl group;
R ⁸ is an alkyl group with 1-4 carbon atoms;
substituents α ¹ are selected from the group consisting of halogen atoms, cyano groups, alkoxy groups with 1-3 carbon atoms, alkylthio groups with 1-3 carbon atoms, alkanoyloxy groups with 2-5 carbon atoms, alkoxycarbonyl groups with 2-4 carbon atoms, carbocyclic aryloxy groups with 6-10 carbon atoms in the ring, carbocyclic arylthio groups with 6-10 carbon atoms in the ring, amino groups, alkanoylamino groups with 2-5 carbon atoms, alkoxycarbonylamino groups with 2-4 carbon atoms, N- (C ₂ -C ₅ alkoxycarbonyl) -N - (C ₁ -C ₃ alkyl) amino, halogen alkoxycarbonylamino groups with 2-5 carbon atoms, carbocyclic arylcarbonylamino groups in which the aryl part has 6-10 carbon atoms in the ring, aralkylcarbonylamino groups in which the aryl part is carbocyclic and has 6-10 carbon atoms in the ring, and the alkyl part contains 1 or 2 atoms carbon, carbocyclic aryl groups with 6-10 carbon atoms in the ring, which may be unsubstituted or substituted by at least one of the substituents γ ¹ , the group R ^h -S, where R ^h represents a heterocyclic group with 3-6 atoms in co liet, of which at least one is a heteroatom of nitrogen and / or oxygen and / or sulfur, wherein said heterocyclic group is not substituted, but alkanoyl groups with 2-5 carbon atoms;
substituents γ ¹ are selected from the group consisting of halogen atoms, cyano groups, nitro groups, alkyl groups with 1-4 carbon atoms, alkoxy groups with 1-4 carbon atoms and alkoxycarbonyl groups with 2-5 carbon atoms. 9. Compounds according to any one of the preceding paragraphs, where R ³ represents an amino group, a methylamino group, an ethyl amino group, an alkoxyl group with 1-3 carbon atoms or a group of the formula (iii), (v) or (vi):

or

in which R ⁴ is an alkyl group with 1-4 carbon atoms, a substituted alkyl group with 1-3 carbon atoms, which is substituted by at least one of the substituents α ² listed below, a cycloalkyl group with 3-6 carbon atoms, an alkenyl group with 3 or 4 carbon atoms, an alkynyl group with 3 or 4 carbon atoms, a carbocyclic aryl group with 6-10 carbon atoms in the ring that may be unsubstituted or substituted by at least one of the substituents γ ¹ listed below, or a heterocyclic group with 3- 6 atoms in the ring, of which Raina least one heteroatom is nitrogen and / or oxygen and / or sulfur, said heterocyclic group may be unsubstituted or substituted by at least one of the following substituents γ ^1, or an oxygen atom;
R ⁵ is as defined above;
r is 1, 2 or 3;
Q is a methylene group or a carbonyl group;
substituents α ² are selected from the group consisting of halogen atoms, cyano groups, methoxy groups, ethoxy groups, methylthio groups, ethylthio groups, alkanoyloxy groups with 2 or 3 carbon atoms, alkoxycarbonyl groups with 2 or 3 carbon atoms, phenoxy groups, phenylthio groups, amino groups, alkanoylamino groups with 2 -5 carbon atoms, alkoxycarbonylamino groups with 2-4 carbon atoms, N- (C ₂ -C ₅ alkoxycarbonyl) -N- (C ₁ -C ₃ -alkyl) amino, haloalkoxycarbonylamino with 2-5 carbon atoms, carbocyclic arilkarbonilaminogru powders in which the aryl part has 6 to 10 carbon atoms in the ring, aralkylcarbonylamino groups in which the aryl part is carbocyclic and has 6 to 10 carbon atoms in the ring, and the alkyl part contains 1 or 2 carbon atoms, phenyl groups that can be unsubstituted or substituted by at least one of the substituents γ ^{2 of the} group R ^h -S, where R ^h represents a heterocyclic group with 3-6 atoms in the ring, of which at least one is a nitrogen and / or oxygen heteroatom, and / or sulfur, wherein said heterocyclic th group is unsubstituted;
γ ² substituents are selected from the group consisting of halogen atoms, cyano groups, nitro groups, methyl groups, ethyl groups, methoxy groups and alkoxycarbonyl groups with 2 or 3 carbon atoms. 10. The compound of claim 9, wherein R ³ is an amino group, methylamino group, ethylamino group, or a group of formula (iii) or (vi):

or

in which R ⁴ is an alkyl group with 1-4 carbon atoms, a substituted alkyl group with 1-3 carbon atoms, which is substituted by at least one of the following substituents α ³ , a cycloalkyl group with 5 or 6 carbon atoms, a phenyl group, which may be unsubstituted or substituted by at least one of the following substituents γ ³ , or a heterocyclic group with 5 or 6 atoms in the ring, of which at least one is a heteroatom of nitrogen and / or oxygen and / or sulfur, wherein a heterocyclic group may be n unsubstituted or substituted by at least one of the following substituents γ ^3;
R ⁵ is as defined above;
r is 2;
Q is a methylene group or a carbonyl group;
substituents α ³ are selected from the group consisting of halogen atoms, cyano groups, methoxy groups, ethoxy groups, alkanoyloxy groups with 2 or 3 carbon atoms, alkoxycarbonyl groups with 2 or 3 carbon atoms, phenoxy groups, amino groups, alkanoylamino groups with 2 or 3 carbon atoms, alkoxycarbonylamino groups with 2-4 carbon atoms and a benzoylcarbonylamino group;
γ ³ substituents are selected from the group consisting of halogen atoms, cyano groups, nitro groups, methyl groups, ethyl groups, methoxy groups and ethoxyl groups.  11. Compounds according to any one of the preceding paragraphs, where n is 0. 12. The compound according to claim 1, which is 13- [2- (4-cyanoacetylaminophenyl) -2-methylpropionyloxy] -5-hydroxyiminomylbemycin A ₄ . 13. The compound according to claim 1, which is 13- {2- [4- (N-acetylglycyl) aminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ . 14. The compound according to claim 1, which is 13- {2- [4- (N-methoxycarbonylglycyl) methylaminophenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ . 15. The compound according to claim 1, which is 13- [2- [4-methoxycarbonylaminophenyl) -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ . 16. The compound according to claim 1, which is 13- {2- [4- (N-phenylcarbamoylamino) phenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ . 17. The compound according to claim 1, which is 13- {2- [4- (2-oxooxazolin-3-yl) phenyl] -2-methylpropionyloxy} -5-hydroxyiminomylbemycin A ₄ . 18. The compound according to claim 1, which is 13- [1- [4-aminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ . 19. The compound according to claim 1, which is a 13- [1- [4-acetylaminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ . 20. The compound according to claim 1, which is a 13- [1- [4-acetoxyacetylaminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ . 21. The compound according to claim 1, which is 13- [1- [4-methanesulfonylaminophenyl) cyclopentanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ . 22. The compound according to claim 1, which is a 13- [1- [4-acetylaminophenyl) -1-ethylbutyryloxy] -5-hydroxyiminomylbemycin A ₄ . 23. The compound according to claim 1, which is a 13- [1- [4-acetylaminophenyl) cyclobutanecarbonyloxy] -5-hydroxyiminomylbemycin A ₄ .  24. An anthelmintic, acaricidal or insecticidal composition containing the active ingredient in a mixture with an excipient or diluent suitable for use in agriculture, characterized in that it contains the compound of formula I or its salt according to any one of paragraphs 1-23 as the active ingredient.

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